Vascular endothelial function in health and diseases.

The vascular endothelium constitutes approximately 1% of body mass (1kg) and has a surface area of approximately 5000m(2). The endothelium is a multifunctional endocrine organ strategically placed between the vessel wall and the circulating blood, and has a key role in vascular homeostasis. The endothelium is both a target for and mediator of cardiovascular disease. The endothelium releases several relaxing and constricting factors, which can affect vascular homeostasis. Endothelial dysfunction, whether caused by physical injury or cellular damage, leads to compensatory responses that alter the normal homeostatic properties of the endothelium. In this review, we summarized some physiological aspects of endothelial function and then we discussed endothelial dysfunction during some pathological conditions.

[1]  C. Garland,et al.  K+ is an endothelium-derived hyperpolarizing factor in rat arteries , 1998, Nature.

[2]  P. Poredos,et al.  Smoking is Associated with Dose-Related Increase of Intima-Media Thickness and Endothelial Dysfunction , 1999, Angiology.

[3]  A. Lerman,et al.  Endothelin in cardiovascular disease: from atherosclerosis to heart failure. , 2000, Journal of cardiovascular pharmacology.

[4]  E. Dejana,et al.  Perspectives Series: Cell Adhesion in Vascular Biology Endothelial Adherens Junctions: Implications in the Control of Vascular Permeability and Angiogenesis , 1996 .

[5]  E. Schiffrin,et al.  Effect of crossing over hypertensive patients from a beta-blocker to an angiotensin receptor antagonist on resistance artery structure and on endothelial function , 2002, Journal of hypertension.

[6]  H. Schelbert,et al.  L-Arginine normalizes coronary vasomotion in long-term smokers. , 1999, Circulation.

[7]  J. Loscalzo,et al.  Endothelial cells in physiology and in the pathophysiology of vascular disorders. , 1998, Blood.

[8]  P. Ortiz de Montellano,et al.  Inhibition of renal vascular 20-HETE production impairs autoregulation of renal blood flow. , 1994, The American journal of physiology.

[9]  V. Miller,et al.  The Effect of Estrogen Replacement Therapy on Plasma Nitric Oxide and Endothelin-1 Levels in Postmenopausal Women , 1998, Annals of Internal Medicine.

[10]  J. Musser,et al.  Phospholipase A2: function and pharmacological regulation. , 1987, Biochemical pharmacology.

[11]  A. Kashiwagi,et al.  Impaired Activation of Glucose Oxidation and NADPH Supply in Human Endothelial Cells Exposed to H2O2 in High-Glucose Medium , 1995, Diabetes.

[12]  P. Vanhoutte,et al.  Interaction between Na+,K+ exchanges and the direct inhibitory effect of acetylcholine on canine femoral arteries. , 1980, Circulation research.

[13]  P. Pratt,et al.  Determination of EETs using microbore liquid chromatography with fluorescence detection. , 2000, American journal of physiology. Heart and circulatory physiology.

[14]  E. Schiffrin,et al.  Antioxidant Effects of Vitamins C and E Are Associated With Altered Activation of Vascular NADPH Oxidase and Superoxide Dismutase in Stroke-Prone SHR , 2001, Hypertension.

[15]  G. Christ,et al.  Gap junctions in vascular tissues. Evaluating the role of intercellular communication in the modulation of vasomotor tone. , 1996, Circulation research.

[16]  T. Lüscher,et al.  Release of endothelin from the porcine aorta. Inhibition by endothelium-derived nitric oxide. , 1990, The Journal of clinical investigation.

[17]  P. Libby,et al.  Immunopathology of coronary arteriosclerosis in transplanted hearts. , 1992, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[18]  Charles Kooperberg,et al.  Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. , 2002, JAMA.

[19]  D. Tollefsen,et al.  Heparin cofactor II activity in patients with disseminated intravascular coagulation and hepatic failure. , 1985, Blood.

[20]  D. Harrison,et al.  Electron Spin Resonance Characterization of Vascular Xanthine and NAD(P)H Oxidase Activity in Patients With Coronary Artery Disease: Relation to Endothelium-Dependent Vasodilation , 2003, Circulation.

[21]  D. Koritnik,et al.  Estrogen pretreatment directly potentiates endothelium-dependent vasorelaxation of porcine coronary arteries. , 1995, The American journal of physiology.

[22]  J. Mcgiff,et al.  Is EDHF an epoxyeicosatrienoic acid? , 2000, Trends in pharmacological sciences.

[23]  R. Kloner,et al.  Beneficial effects of captopril in acute coxsackievirus B3 murine myocarditis. , 1990, Circulation.

[24]  H. Drexler,et al.  Vascular extracellular superoxide dismutase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. , 2000, Circulation.

[25]  S. Krungkrai,et al.  Exogenous advanced glycosylation end products induce complex vascular dysfunction in normal animals: a model for diabetic and aging complications. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[26]  R. Weisbrod,et al.  Effect of elevated glucose on cyclic GMP and eicosanoids produced by porcine aortic endothelium. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[27]  S. G. Taylor,et al.  Endothelium-derived hyperpolarizing a new endogenous inhibitor from the vascular endothelium , 1988 .

[28]  P. Vanhoutte Endothelial control of vasomotor function: from health to coronary disease. , 2003, Circulation journal : official journal of the Japanese Circulation Society.

[29]  A. Koller,et al.  Superoxide-NO interaction decreases flow- and agonist-induced dilations of coronary arterioles in Type 2 diabetes mellitus. , 2003, American journal of physiology. Heart and circulatory physiology.

[30]  A. Quyyumi,et al.  Effect of antihypertensive treatment on endothelium-dependent vascular relaxation in patients with essential hypertension. , 1993, Journal of the American College of Cardiology.

[31]  B. McManus,et al.  Profound inhibition of myogenic tone in rat cardiac allografts is due to eNOS- and iNOS-based nitric oxide and an intrinsic defect in vascular smooth muscle contraction. , 2000, Circulation.

[32]  M. Lingen,et al.  Role of leukocytes and endothelial cells in the development of angiogenesis in inflammation and wound healing. , 2001, Archives of pathology & laboratory medicine.

[33]  A. Quyyumi,et al.  Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. , 1990, The New England journal of medicine.

[34]  J. Vane,et al.  The Fate of Radioiodinated Endothelin‐1 and Endothelin‐3 in the Rat , 1989, Journal of cardiovascular pharmacology.

[35]  W. Aird,et al.  The endothelium and thrombosis. , 2000, Seminars in thrombosis and hemostasis.

[36]  S. Mutalik,et al.  Glibenclamide transdermal patches: physicochemical, pharmacodynamic, and pharmacokinetic evaluations. , 2004, Journal of pharmaceutical sciences.

[37]  É. Moreira,et al.  Exercise training changes autonomic cardiovascular balance in mice. , 2004, Journal of applied physiology.

[38]  R. Alexander,et al.  Relevance of vascular biology to the ischemic syndromes of coronary atherosclerosis , 2004, Cardiovascular Drugs and Therapy.

[39]  R. Busse,et al.  Cytochrome P450 2C is an EDHF synthase in coronary arteries , 1999, Nature.

[40]  R. Furchgott,et al.  The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine , 1980, Nature.

[41]  A. Malik,et al.  Regulation of vascular endothelial barrier function. , 1994, The American journal of physiology.

[42]  B. McManus,et al.  Augmented Contractile Response of Vascular Smooth Muscle in a Diabetic Mouse Model , 2003, Journal of Vascular Research.

[43]  P. Kubes,et al.  Nitric oxide: an endogenous modulator of leukocyte adhesion. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[44]  J. Mcgiff,et al.  20-Hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids and blood pressure , 2001, Current opinion in nephrology and hypertension.

[45]  D. Stepp,et al.  Oxidant stress-induced increase in myogenic activation of skeletal muscle resistance arteries in obese Zucker rats. , 2002, American journal of physiology. Heart and circulatory physiology.

[46]  C. Temm,et al.  Exercise acutely increases circulating endothelial progenitor cells and monocyte-/macrophage-derived angiogenic cells. , 2004, Journal of the American College of Cardiology.

[47]  M. Molnar,et al.  Signal transduction in rat myometrial cells: comparison of the actions of endothelin-1, oxytocin and prostaglandin F2 alpha. , 1995, European journal of endocrinology.

[48]  S. Moncada,et al.  Nitric oxide: physiology, pathophysiology, and pharmacology. , 1991, Pharmacological reviews.

[49]  M. Khazaei,et al.  Sulfaphenazole treatment restores endothelium-dependent vasodilation in diabetic mice. , 2008, Vascular pharmacology.

[50]  T. Imaizumi,et al.  Tetrahydrobiopterin restores endothelial function in long-term smokers. , 2000, Journal of the American College of Cardiology.

[51]  W. Mayhan,et al.  Effect of nicotine on endothelium-dependent arteriolar dilatation in vivo. , 1997, The American journal of physiology.

[52]  J. Loscalzo,et al.  Inhibition of neointimal proliferation in rabbits after vascular injury by a single treatment with a protein adduct of nitric oxide. , 1995, The Journal of clinical investigation.

[53]  P. Pratt,et al.  Endothelium-independent, ouabain-sensitive relaxation of bovine coronary arteries by EETs. , 2001, American journal of physiology. Heart and circulatory physiology.

[54]  J. Keaney,et al.  The clinical implications of endothelial dysfunction. , 2003, Journal of the American College of Cardiology.

[55]  Yohnosuke Kobayashi,et al.  Endothelin-1 Has a Priming Effect on Production of Superoxide Anion by Alveolar Macrophages: Its Possible Correlation with Bronchopulmonary Dysplasia , 1996, Pediatric Research.

[56]  D. Harrison,et al.  Endothelial Regulation of Vasomotion in ApoE-Deficient Mice: Implications for Interactions Between Peroxynitrite and Tetrahydrobiopterin , 2001, Circulation.

[57]  W. Roberts,et al.  Intramural ("small vessel") coronary artery disease in hypertrophic cardiomyopathy. , 1986, Journal of the American College of Cardiology.

[58]  M. Khazaei,et al.  Effect of exercise on augmented aortic vasoconstriction in the db/db mouse model of type-II diabetes. , 2008, Physiological research.

[59]  Office on Smoking The Health Consequences of Smoking , 2004 .

[60]  O. Hess,et al.  Tetrahydrobiopterin improves endothelial function in patients with coronary artery disease. , 2000, Journal of cardiovascular pharmacology.

[61]  R. Ross Atherosclerosis is an inflammatory disease , 1999 .

[62]  J. Vane,et al.  Prostacyclin: a vascular mediator. , 2003, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[63]  J. Hoover-Plow,et al.  The cell biology of the plasminogen system , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[64]  B. McManus,et al.  Endothelial and myogenic regulation of coronary artery tone in the mouse. , 2000, European journal of pharmacology.

[65]  B. McManus,et al.  Coxsackievirus B3 Infection Compromises Endothelial-Dependent Vasodilation of Coronary Resistance Arteries , 2004, Journal of cardiovascular pharmacology.

[66]  V. Hinsbergh,et al.  The endothelium: vascular control of haemostasis , 2001 .

[67]  E. Schiffrin,et al.  Expression of a Functionally Active gp91phox-Containing Neutrophil-Type NAD(P)H Oxidase in Smooth Muscle Cells From Human Resistance Arteries: Regulation by Angiotensin II , 2002, Circulation research.

[68]  C. Hill,et al.  Incidence of myoendothelial gap junctions in the proximal and distal mesenteric arteries of the rat is suggestive of a role in endothelium-derived hyperpolarizing factor-mediated responses. , 2000, Circulation research.

[69]  R. J. Bala,et al.  Endothelin-1 and endothelin-4 stimulate monocyte production of cytokines. , 1997, Critical care medicine.

[70]  E. Schiffrin,et al.  Correlation of endothelial function in large and small arteries in human essential hypertension. , 2001, Journal of hypertension.

[71]  B. McManus,et al.  Perforin mediates endothelial cell death and resultant transplant vascular disease in cardiac allografts. , 2004, The American journal of pathology.

[72]  C. Triggle,et al.  ENDOTHELIUM‐DERIVED HYPERPOLARIZING FACTOR(S): SPECIES AND TISSUE HETEROGENEITY , 1999, Clinical and experimental pharmacology & physiology.

[73]  F O Mueller,et al.  Sudden death in young competitive athletes. Clinical, demographic, and pathological profiles. , 1996, JAMA.

[74]  B. McManus,et al.  Human transplant coronary artery disease: pathological evidence for Fas-mediated apoptotic cytotoxicity in allograft arteriopathy. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[75]  William R. Burns,et al.  Interferon‐γ plays a nonredundant role in mediating T‐cell‐ dependent outward vascular remodeling of allogeneic human coronary arteries , 2004 .

[76]  M. Nelson,et al.  Extracellular K(+)‐induced hyperpolarizations and dilatations of rat coronary and cerebral arteries involve inward rectifier K(+) channels. , 1996, The Journal of physiology.

[77]  T. Griffith Endothelium‐dependent smooth muscle hyperpolarization: do gap junctions provide a unifying hypothesis? , 2004, British journal of pharmacology.

[78]  M. Khazaei,et al.  Serum level of vascular endothelial growth factor is increased by estrogen replacement therapy in normotensive and DOCA-Salt hypertensive ovariectomized rats. , 2006, Clinica chimica acta; international journal of clinical chemistry.

[79]  J. Loscalzo,et al.  Inhibition of fibrinogen binding to human platelets by S-nitroso-N-acetylcysteine. , 1990, The Journal of biological chemistry.

[80]  J. Czernin,et al.  Cigarette smoking and coronary blood flow. , 2003, Progress in cardiovascular diseases.

[81]  N. Gilula,et al.  The Gap Junction Communication Channel , 1996, Cell.

[82]  T. Kigoshi,et al.  Increased basal levels of plasma nitric oxide in Type 2 diabetic subjects. Relationship to microvascular complications. , 2001, Journal of diabetes and its complications.

[83]  A. Zeiher,et al.  Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. , 1995, Circulation.

[84]  H. Coleman,et al.  Prostacyclin and endothelium-dependent hyperpolarization. , 2004, Pharmacological research.

[85]  M. Khazaei,et al.  The effect of estrogen on serum nitric oxide concentrations in normotensive and DOCA Salt hypertensive ovariectomized rats. , 2004, Clinica chimica acta; international journal of clinical chemistry.

[86]  P. Ganz,et al.  Endothelial function. From vascular biology to clinical applications. , 2002, The American journal of cardiology.

[87]  Xiaowei Liu,et al.  Thrombogenic Effects of Antiphospholipid Antibodies Are Mediated by Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and P-Selectin , 2001, Circulation research.

[88]  G. Broze,et al.  Tissue Factor Pathway Inhibitor , 1995, Thrombosis and Haemostasis.

[89]  R Busse,et al.  Crucial role of endothelium in the vasodilator response to increased flow in vivo. , 1986, Hypertension.

[90]  M. Tuck Nitric oxide in diabetes mellitus. , 2003, Journal of hypertension.

[91]  T. Terao,et al.  Endothelin-1 evoked an increase and oscillations in cytosolic calcium concentration in adherent single human platelets and increased GMP-140 (P-selectin) in platelet suspension. , 1995, Thrombosis research.

[92]  A. Zeiher,et al.  Angiotensin II induces apoptosis of human endothelial cells. Protective effect of nitric oxide. , 1997, Circulation research.

[93]  W. Fleming The electrogenic Na+, K+-pump in smooth muscle: physiologic and pharmacologic significance. , 1980, Annual review of pharmacology and toxicology.

[94]  J. Wang,et al.  Cigarette smoke activates caspase-3 to induce apoptosis of human umbilical venous endothelial cells. , 2001, Molecular genetics and metabolism.

[95]  P. Carmeliet,et al.  Targeted Deficiency or Cytosolic Truncation of the VE-cadherin Gene in Mice Impairs VEGF-Mediated Endothelial Survival and Angiogenesis , 1999, Cell.

[96]  R. Michler,et al.  Overexpression of Soluble Fas Attenuates Transplant Arteriosclerosis in Rat Aortic Allografts , 2002, Circulation.

[97]  R. Bucala,et al.  Tobacco smoke is a source of toxic reactive glycation products. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[98]  L. Ghiadoni,et al.  Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients. , 1996, Circulation.

[99]  K. Kamata,et al.  Decreased Ca2+ influx into the endothelium contributes to the decrease in endothelium-dependent relaxation in the aorta of streptozotocin-induced diabetic mice. , 1995, Research communications in molecular pathology and pharmacology.

[100]  R. Andriantsitohaina,et al.  Age-related endothelial dysfunction with respect to nitric oxide, endothelium-derived hyperpolarizing factor and cyclooxygenase products. , 2000, Physiological research.

[101]  G. Rosano,et al.  Estrogen acutely increases peripheral blood flow in postmenopausal women. , 1995, The American journal of medicine.

[102]  A. Dominiczak,et al.  Is hydrogen peroxide an EDHF in human radial arteries? , 2001, American journal of physiology. Heart and circulatory physiology.

[103]  H Shimokawa,et al.  Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice. , 2000, The Journal of clinical investigation.

[104]  J A Thompson,et al.  Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[105]  P. Guiteras,et al.  Coronary endothelial dysfunction as a predictor of intimal thickening in the long term after heart transplantation. , 2001, The Journal of thoracic and cardiovascular surgery.

[106]  O. Carretero,et al.  The Loss of Endothelium‐Dependent Vascular Relaxation in Hypertension , 1986, Hypertension.

[107]  E. Schiffrin,et al.  Small artery remodeling is the most prevalent (earliest?) form of target organ damage in mild essential hypertension , 2001, Journal of hypertension.

[108]  D. Harrison,et al.  Oxidant stress as a marker for cardiovascular events: Ox marks the spot. , 2001, Circulation.

[109]  K. Willecke,et al.  Impaired conduction of vasodilation along arterioles in connexin40-deficient mice. , 2000, Circulation research.

[110]  Y. Yasukochi,et al.  Recombinant Annexin II Modulates Impaired Fibrinolytic Activity In Vitro and in Rat Carotid Artery , 2001, Circulation research.

[111]  M. Kohno,et al.  Correlation of functional and structural alterations of the coronary arterioles during development of type II diabetes mellitus in rats. , 2002, Cardiovascular research.

[112]  C. Triggle,et al.  Endothelium-derived relaxing factors: a focus on endothelium-derived hyperpolarizing factor(s). , 2001, Canadian journal of physiology and pharmacology.

[113]  J. Falck,et al.  Cytochrome P450, the arachidonic acid cascade, and hypertension: new vistas for an old enzyme system , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[114]  B. McManus,et al.  Ultrastructural evidence of early endothelial damage in coronary arteries of rat cardiac allografts. , 2003, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[115]  L. Ignarro,et al.  Cigarette smoking increases endothelial-derived vasorelaxation in the rat carotid artery in a dose-dependent manner. , 1997, The Journal of surgical research.

[116]  P. Poole‐Wilson,et al.  Endothelium‐independent relaxation of rabbit coronary artery by 17β‐oestradiol in vitro , 1991, British journal of pharmacology.

[117]  M. Khazaei,et al.  Coronary vascular and aortic endothelial permeability during estrogen therapy: a study in DOCA-salt hypertensive ovariectomized rats. , 2004, Physiological research.

[118]  James T. Willerson,et al.  Direct Proinflammatory Effect of C-Reactive Protein on Human Endothelial Cells , 2000, Circulation.

[119]  W. Baumgartner,et al.  Cardiac allograft vasculopathy: the central pathogenetic role of ischemia-induced endothelial cell injury. , 1995, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[120]  D. Celermajer,et al.  Endothelial dysfunction: does it matter? Is it reversible? , 1997, Journal of the American College of Cardiology.

[121]  R D Fish,et al.  Endothelium-dependent dilation of the coronary microvasculature is impaired in dilated cardiomyopathy. , 1990, Circulation.

[122]  G. G. Emerson,et al.  Electrical activation of endothelium evokes vasodilation and hyperpolarization along hamster feed arteries. , 2001, American journal of physiology. Heart and circulatory physiology.

[123]  P. Serruys,et al.  Decreased coronary flow reserve in hypertrophic cardiomyopathy is related to remodeling of the coronary microcirculation. , 1998, Circulation.

[124]  I. Ginsburg,et al.  Endothelial cell killing by neutrophils. Synergistic interaction of oxygen products and proteases. , 1989, The American journal of pathology.

[125]  C. Dhabuwala,et al.  Cigarette smoking induces apoptosis in rat testis. , 2002, Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer.

[126]  M. Endres,et al.  Physical Training Increases Endothelial Progenitor Cells, Inhibits Neointima Formation, and Enhances Angiogenesis , 2004 .

[127]  S. Rajagopalan,et al.  Altered Tetrahydrobiopterin Metabolism in Atherosclerosis: Implications for Use of Oxidized Tetrahydrobiopterin Analogues and Thiol Antioxidants , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[128]  R. Cohen,et al.  Contraction of diabetic rabbit aorta caused by endothelium-derived PGH2-TxA2. , 1989, The American journal of physiology.

[129]  P. Klatt,et al.  Increased Adhesion and Aggregation of Platelets Lacking Cyclic Guanosine 3′,5′-Monophosphate Kinase I , 1999, The Journal of experimental medicine.

[130]  R. Barst,et al.  Endothelin receptor antagonists in pulmonary arterial hypertension. , 2004, Journal of the American College of Cardiology.

[131]  G. Edwards,et al.  EDHF – are there gaps in the pathway? , 2001, The Journal of physiology.

[132]  A. Ferro,et al.  S-Nitrosothiols: a class of nitric oxide-donor drugs. , 2000, Clinical science.

[133]  Haruchika Masuda,et al.  Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization , 1999, Nature Medicine.

[134]  A. Hudetz,et al.  Production of 20-HETE and its role in autoregulation of cerebral blood flow. , 2000, Circulation research.

[135]  A. Hassid,et al.  Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. , 1989, The Journal of clinical investigation.

[136]  M. Hoeper,et al.  Endothelin receptor antagonists in pulmonary arterial hypertension , 2008, European Respiratory Journal.

[137]  B. Lipworth,et al.  Cardiopulmonary effects of endothelin-1 in man. , 1997, Cardiovascular research.

[138]  S. Sasayama,et al.  Lysophosphatidylcholine inhibits endothelium-dependent hyperpolarization and N omega-nitro-L-arginine/indomethacin-resistant endothelium-dependent relaxation in the porcine coronary artery. , 1995, Circulation.

[139]  D. Loskutoff,et al.  The Prothrombotic Effects of Leptin , 2001 .

[140]  C. Cho,et al.  The role of nitric oxide on cigarette smoke-induced programmed cell death in the gastric mucosa. , 2000, Scandinavian journal of gastroenterology.

[141]  P. Tsao,et al.  NOS inhibition accelerates atherogenesis: reversal by exercise. , 2003, American journal of physiology. Heart and circulatory physiology.

[142]  J S Beckman,et al.  Mechanisms of cerebral vasodilation by superoxide, hydrogen peroxide, and peroxynitrite. , 1996, The American journal of physiology.

[143]  C. Esmon Regulation of blood coagulation. , 2000, Biochimica et biophysica acta.

[144]  W. Sessa,et al.  T cell-mediated vascular dysfunction of human allografts results from IFN-gamma dysregulation of NO synthase. , 2004, The Journal of clinical investigation.

[145]  U. Förstermann,et al.  Estrogens increase transcription of the human endothelial NO synthase gene: analysis of the transcription factors involved. , 1998, Hypertension.

[146]  H. Granger,et al.  Nitric Oxide Is an Upstream Signal of Vascular Endothelial Growth Factor-induced Extracellular Signal-regulated Kinase½ Activation in Postcapillary Endothelium* , 1998, The Journal of Biological Chemistry.

[147]  H. Drexler,et al.  Endothelial function: a critical determinant in atherosclerosis? , 2004, Circulation.

[148]  Richard E. White,et al.  H2O2 opens BKCa channels via the PLA2-arachidonic acid signaling cascade in coronary artery smooth muscle , 2000 .

[149]  J. Tamaoki,et al.  Acute cigarette smoke exposure induces apoptosis of alveolar macrophages. , 2001, American journal of physiology. Lung cellular and molecular physiology.

[150]  G. Garcı́a-Cardeña,et al.  17 beta-estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca2+ mobilization. , 1997, Circulation research.

[151]  R. A. Coleman,et al.  Characterization of dilator prostanoid receptors in the fetal rabbit ductus arteriosus. , 1994, The Journal of pharmacology and experimental therapeutics.

[152]  J. McMurray,et al.  Endothelium-Derived Hyperpolarizing Factor: Identification and Mechanisms of Action in Human Subcutaneous Resistance Arteries , 2001, Circulation.

[153]  E. Jackson,et al.  Circulating nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17 beta-estradiol and norethisterone acetate. A two-year follow-up study. , 1995, Hypertension.

[154]  J. Masferrer,et al.  Role of cyclooxygenases in angiogenesis. , 2000, Current medicinal chemistry.

[155]  N. Standen,et al.  Arterial dilations in response to calcitonin gene-related peptide involve activation of K+ channels , 1990, Nature.

[156]  B. McManus,et al.  Cyclosporine treatment preserves coronary resistance artery function in rat cardiac allografts. , 2004, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[157]  L. Kaijser,et al.  Comparable potent coronary constrictor effects of endothelin-1 and big endothelin-1 in humans. , 1996, Circulation.

[158]  E. Schiffrin,et al.  Correction of arterial structure and endothelial dysfunction in human essential hypertension by the angiotensin receptor antagonist losartan. , 2000, Circulation.

[159]  D. Isenberg,et al.  IgG anti-endothelial cell autoantibodies from patients with systemic lupus erythematosus or systemic vasculitis stimulate the release of two endothelial cell-derived mediators, which enhance adhesion molecule expression and leukocyte adhesion in an autocrine manner. , 1999, Arthritis and rheumatism.

[160]  A. Dominiczak,et al.  Investigation into the sources of superoxide in human blood vessels: angiotensin II increases superoxide production in human internal mammary arteries. , 2000, Circulation.

[161]  M. Matsuda,et al.  Quantitative analysis of narrowings of intramyocardial small arteries in normal hearts, hypertensive hearts, and hearts with hypertrophic cardiomyopathy. , 1987, Circulation.

[162]  S. Albelda,et al.  Integrins and other cell adhesion molecules , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[163]  J. Vane,et al.  Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2, and prostacyclin. , 1978, Pharmacological reviews.

[164]  W. Mayhan Acute infusion of nicotine potentiates norepinephrine-induced vasoconstriction in the hamster cheek pouch. , 1999, The Journal of laboratory and clinical medicine.

[165]  Hong Yang,et al.  Effects of age and food restriction on oxidative DNA damage and antioxidant enzyme activities in the mouse aorta , 2001, Mechanisms of Ageing and Development.

[166]  Shuxia Wang,et al.  Nitric Oxide and cGMP-dependent Protein Kinase Regulation of Glucose-mediated Thrombospondin 1-dependent Transforming Growth Factor-β Activation in Mesangial Cells* , 2002, The Journal of Biological Chemistry.

[167]  S. Dohi,et al.  Mechanisms underlying cerebrovascular effects of cigarette smoking in rats in vivo. , 1998, Stroke.

[168]  T. Lincoln,et al.  Pleiotropic regulation of vascular smooth muscle tone by cyclic GMP-dependent protein kinase. , 1994, Hypertension.

[169]  J. Granger,et al.  Role of Endothelin B Receptors in Enhancing Endothelium-Dependent Nitric Oxide–Mediated Vascular Relaxation During High Salt Diet , 2001, Hypertension.

[170]  P. Vanhoutte Endothelium-dependent hyperpolarizations: the history. , 2004, Pharmacological research.

[171]  P. Kalman,et al.  Clinical and pathophysiological effects of active and passive smoking on the cardiovascular system. , 1998, The Canadian journal of cardiology.

[172]  B. Battistini,et al.  Effect of ECE and NEP inhibition on cigarette smoke-induced cell proliferation in the rat lung. , 2001, Inhalation toxicology.

[173]  L. Ghiadoni,et al.  Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. , 1998, Circulation.

[174]  S. Verma,et al.  Chronic oral supplementation with sepiapterin prevents endothelial dysfunction and oxidative stress in small mesenteric arteries from diabetic (db/db) mice , 2003, British journal of pharmacology.

[175]  M. Nelson,et al.  Gender differences in coronary artery diameter reflect changes in both endothelial Ca2+ and ecNOS activity. , 1999, The American journal of physiology.

[176]  E. Masih-Khan,et al.  Influence of Type II Diabetes on Arterial Tone and Endothelial Function in Murine Mesenteric Resistance Arteries , 2001, Journal of Vascular Research.

[177]  A. Laroia,et al.  Endothelium and the lipid metabolism: the current understanding. , 2003, International journal of cardiology.

[178]  Hiroshi Takahashi,et al.  Enhanced inhibition of hepatitis B virus production by asialoglycoprotein receptor-directed interferon , 1999, Nature Medicine.

[179]  D. Herrington,et al.  Endothelial-dependent coronary vasomotor responsiveness in postmenopausal women with and without estrogen replacement therapy. , 1994, The American journal of cardiology.

[180]  E. Bassenge,et al.  Coronary vasomotor responses: Role of endothelium and nitrovasodilators , 1994, Cardiovascular Drugs and Therapy.

[181]  A. Rahmel,et al.  The Registry of the International Society for Heart and Lung Transplantation: thirteenth official pediatric heart transplantation report--2010. , 2010, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[182]  T. Lüscher,et al.  High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. , 1997, Circulation.

[183]  A. Koch,et al.  Chemokines and angiogenesis , 2001, Current opinion in rheumatology.

[184]  Z. Krajcer,et al.  Coronary artery disease in hypertrophic cardiomyopathy. , 1985, The American journal of cardiology.

[185]  H. Granger,et al.  VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. , 1998, American journal of physiology. Heart and circulatory physiology.

[186]  J. Piette,et al.  The binding of some human antiendothelial cell antibodies induces endothelial cell apoptosis. , 1998, The Journal of clinical investigation.

[187]  R. Novick,et al.  The Registry of the International Society for Heart and Lung Transplantation: fifteenth official report--1998. , 1998, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[188]  T. Amachi,et al.  Expression of a hybrid Cu/Zn-type superoxide dismutase which has high affinity for heparin-like proteoglycans on vascular endothelial cells. , 1991, The Journal of biological chemistry.

[189]  R. Busse,et al.  Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation , 1999, Nature.

[190]  J. Marcum,et al.  Anticoagulantly active heparin-like molecules from vascular tissue. , 1984, Biochemistry.

[191]  J. Powell,et al.  Smoking impairs the activity of endothelial nitric oxide synthase in saphenous vein. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[192]  G. Winkler,et al.  Characteristics of coronary endothelial dysfunction in experimental diabetes. , 1997, Cardiovascular research.

[193]  Carine Michiels,et al.  Endothelial cell functions , 2003, Journal of cellular physiology.

[194]  N. Standen,et al.  The Role of the Membrane Potential of Endothelial and Smooth Muscle Cells in the Regulation of Coronary Blood Flow , 1994, Journal of cardiovascular electrophysiology.

[195]  B. Feldt-Rasmussen,et al.  FEATURES OF ENDOTHELIAL DYSFUNCTION IN EARLY DIABETIC NEPHROPATHY , 1989, The Lancet.

[196]  M. Toborek,et al.  Endothelial cell functions.¶Relationship to atherogenesis , 1999, Basic Research in Cardiology.

[197]  M. Tominaga,et al.  The effect of alpha 1-blocker, bunazosin on a murine model of congestive heart failure induced by viral myocarditis. , 1992, Japanese circulation journal.

[198]  B. Strauer,et al.  Evidence of endothelial dysfunction of epicardial coronary arteries in patients with immunohistochemically proven myocarditis. , 1998, American heart journal.

[199]  M. Yanagisawa,et al.  The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[200]  B. Freeman,et al.  Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[201]  B. McManus,et al.  Coronary artery myogenic response in a genetic model of hypertrophic cardiomyopathy. , 2002, American journal of physiology. Heart and circulatory physiology.

[202]  E. Schiffrin,et al.  Multiple actions of angiotensin II in hypertension , 2003 .

[203]  K. Nakao,et al.  Plasma Endothelin Concentrations in Patients With Pulmonary Hypertension Associated With Congenital Heart Defects: Evidence for Increased Production of Endothelin in Pulmonary Circulation , 1991, Circulation.

[204]  A. Koch,et al.  Angiogenesis in rheumatoid arthritis: pathogenic and clinical significance. , 1998, Journal of investigative medicine : the official publication of the American Federation for Clinical Research.

[205]  A M Zeiher,et al.  HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. , 2001, The Journal of clinical investigation.

[206]  A. Malik,et al.  Mechanisms of increased endothelial permeability. , 1996, Canadian journal of physiology and pharmacology.

[207]  M. Sole,et al.  Verapamil ameliorates the clinical and pathological course of murine myocarditis. , 1992, The Journal of clinical investigation.

[208]  I. Laher,et al.  Oxidized Low-density Lipoprotein Inhibits Endothelium-dependent Vasodilation by an Antioxidant-sensitive, Lysophosphatidylcholine-independent Mechanism , 2003, Journal of cardiovascular pharmacology.

[209]  Steven M Holland,et al.  Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. , 2003, The Journal of clinical investigation.

[210]  D. Harrison,et al.  Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. , 2000, Circulation research.

[211]  T. Carlos,et al.  Leukocyte-endothelial adhesion molecules. , 1994, Blood.

[212]  G. G. Emerson,et al.  Electrical Coupling Between Endothelial Cells and Smooth Muscle Cells in Hamster Feed Arteries: Role in Vasomotor Control , 2000, Circulation research.

[213]  S. Gross,et al.  Nitric oxide: pathophysiological mechanisms. , 1995, Annual review of physiology.

[214]  G. Pieper Review of alterations in endothelial nitric oxide production in diabetes: protective role of arginine on endothelial dysfunction. , 1998, Hypertension.

[215]  K. Kugiyama,et al.  Impairment of endothelium-dependent relaxation of rabbit aortas by cigarette smoke extract--role of free radicals and attenuation by captopril. , 1997, Atherosclerosis.

[216]  L. Badimón,et al.  Atherogenic concentrations of native low-density lipoproteins down-regulate nitric-oxide-synthase mRNA and protein levels in endothelial cells. , 1998, European journal of biochemistry.

[217]  A. Koch,et al.  Angiogenesis: Implications for rheumatoid arthritis , 1998 .

[218]  S. Ralston,et al.  Estrogen upregulates endothelial constitutive nitric oxide synthase expression in human osteoblast-like cells. , 1998, Endocrinology.

[219]  P. Klatt,et al.  Defective smooth muscle regulation in cGMP kinase I‐deficient mice , 1998, The EMBO journal.

[220]  J. Hoidal,et al.  Selective increase of antioxidant enzyme activity in the alveolar macrophages from cigarette smokers and smoke-exposed hamsters. , 1990, The American review of respiratory disease.

[221]  H. Zerwes,et al.  TRANSPLANTATION-INDUCED ENDOTHELIAL DYSFUNCTION AS STUDIED IN RAT AORTA ALLOGRAFTS , 2001, Transplantation.

[222]  C. Garland,et al.  Properties of smooth muscle hyperpolarization and relaxation to K+ in the rat isolated mesenteric artery. , 2001, American journal of physiology. Heart and circulatory physiology.

[223]  S. Narumiya,et al.  International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. , 1994, Pharmacological reviews.

[224]  J. Mcgiff,et al.  20-HETE and the kidney: resolution of old problems and new beginnings. , 1999, The American journal of physiology.

[225]  P. Halushka,et al.  Thromboxane, prostaglandin and leukotriene receptors. , 1989, Annual review of pharmacology and toxicology.

[226]  R Bicknell,et al.  Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. , 1997, The Journal of clinical investigation.

[227]  S. Hayashi,et al.  Cytosolic calcium increase in coronary endothelial cells after H2O2 exposure and the inhibitory effect of U78517F , 1992, British journal of pharmacology.

[228]  Timothy A. Springer,et al.  Adhesion receptors of the immune system , 1990, Nature.

[229]  K. Kugiyama,et al.  Does passive smoking impair endothelium-dependent coronary artery dilation in women? , 1998, Journal of the American College of Cardiology.

[230]  A. Matsumori,et al.  Contribution of endothelin-1 to myocardial injury in a murine model of myocarditis: acute effects of bosentan, an endothelin receptor antagonist. , 1999, Circulation.

[231]  M. Phelps,et al.  Effects of long-term smoking on myocardial blood flow, coronary vasomotion, and vasodilator capacity. , 1998, Circulation.

[232]  T. Katagiri,et al.  Ultrastructural changes of blood capillaries in patients with microvascular angina, hypertrophic cardiomyopathy, and dilated cardiomyopathy. , 1995, The American journal of cardiovascular pathology.

[233]  E. Stankevičius,et al.  [Role of nitric oxide and other endothelium-derived factors]. , 2003, Medicina.

[234]  N R Webster,et al.  Physiology of the endothelium. , 2004, British journal of anaesthesia.

[235]  P. McBride,et al.  The health consequences of smoking. Cardiovascular diseases. , 1992, The Medical clinics of North America.

[236]  S. Koschnick,et al.  Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity. , 2001, The Journal of clinical investigation.

[237]  M. Limburg,et al.  PREDISPOSITION FOR ATOPY OR ALLERGY LINKED TO HL-A , 1975, The Lancet.

[238]  Richard E. White,et al.  Hydrogen peroxide relaxes porcine coronary arteries by stimulating BKCachannel activity. , 1998, American journal of physiology. Heart and circulatory physiology.

[239]  A. Lerman,et al.  The endothelium: Dysfunction and beyond , 2001, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[240]  E. Anggard,et al.  Antioxidants, diabetes and endothelial dysfunction. , 2000, Cardiovascular research.

[241]  C. Vahl,et al.  Endothelial Dysfunction of Coronary Resistance Arteries Is Improved by Tetrahydrobiopterin in Atherosclerosis , 2000, Circulation.

[242]  S Hulley,et al.  Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. , 1998, JAMA.

[243]  R. Gryglewski Prostacyclin as a circulatory hormone. , 1979, Biochemical pharmacology.

[244]  C. Triggle,et al.  Endothelium-derived reactive oxygen species: their relationship to endothelium-dependent hyperpolarization and vascular tone. , 2003, Canadian journal of physiology and pharmacology.

[245]  D. Harrison,et al.  Mechanisms Underlying Endothelial Dysfunction in Diabetes Mellitus , 2001 .

[246]  B. McManus,et al.  Long-term effects of ovariectomy and estrogen replacement treatment on endothelial function in mature rats. , 2003, Maturitas.

[247]  S. Moncada,et al.  The anti‐aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide , 1987, British journal of pharmacology.

[248]  S. Moncada,et al.  Vascular endothelial cells synthesize nitric oxide from L-arginine , 1988, Nature.

[249]  K. Macleod,et al.  Protein kinase C‐mediated contractile responses of arteries from diabetic rats , 1990, British journal of pharmacology.

[250]  G. G. Emerson,et al.  Endothelial cell pathway for conduction of hyperpolarization and vasodilation along hamster feed artery. , 2000, Circulation research.

[251]  U. Förstermann,et al.  Endothelial Nitric Oxide Synthase in Vascular Disease: From Marvel to Menace , 2006, Circulation.