Testing for endothelial dysfunction

Endothelial health is a key factor in normal cardiovascular homeostasis, and recent studies have revealed several important functions of the vascular endothelium that protect against atherothrombosis. These include control over arterial tone, coagulation, fibrinolysis, and vascular growth. Consequently, endothelial dysfunction has been implicated as an important event in the pathogenesis of atherosclerosis, coronary vasoconstriction, hypertension, and myocardial ischaemia. Therefore, there has been considerable research interest in diagnostic assays for the assessment of endothelium. This review outlines the current status of markers of endothelial dysfunction, particularly those related to vasomotor control, as well as circulating markers of vascular health.

[1]  E. Jaffe,et al.  Cell biology of endothelial cells. , 1987, Human pathology.

[2]  M. Sampson,et al.  Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels. , 1996, Journal of the American College of Cardiology.

[3]  T. Ogihara,et al.  Impaired endothelial function with essential hypertension assessed by ultrasonography. , 1996, American heart journal.

[4]  C. McCollum,et al.  Reduction in cholesterol is associated with reduction in Von Willebrand factor , 1993 .

[5]  A. Lerman,et al.  The role of endothelin in coronary atherosclerosis. , 1996, Mayo Clinic proceedings.

[6]  J. Viikari,et al.  Coronary flow reserve in young men with familial combined hyperlipidemia. , 1999, Circulation.

[7]  V. Salomaa,et al.  Association of fibrinolytic parameters with early atherosclerosis. The ARIC Study. Atherosclerosis Risk in Communities Study. , 1995, Circulation.

[8]  D. Spiegelhalter,et al.  Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility. , 1995, British heart journal.

[9]  E. Nabel,et al.  Atherosclerosis influences the vasomotor response of epicardial coronary arteries to exercise. , 1989, The Journal of clinical investigation.

[10]  Carter Vb,et al.  The power of words. , 1951, Lancet.

[11]  J. Viikari,et al.  Coronary flow reserve is impaired in young men with familial hypercholesterolemia. , 1996, Journal of the American College of Cardiology.

[12]  R. Machovich Choices among the Possible Reaction Routes Catalyzed by Thrombin a , 1986, Annals of the New York Academy of Sciences.

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

[14]  J. K. Lloyd,et al.  Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis , 1992, The Lancet.

[15]  D. Celermajer,et al.  Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. , 1994, Journal of the American College of Cardiology.

[16]  D. Webb,et al.  Endothelial dysfunction, impaired endogenous fibrinolysis, and cigarette smoking: a mechanism for arterial thrombosis and myocardial infarction. , 1999, Circulation.

[17]  A. Lerman,et al.  Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis. , 1991, The New England journal of medicine.

[18]  S. Bode-Böger,et al.  Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease. , 1997, Circulation.

[19]  K. Woo,et al.  Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans. , 1997, Circulation.

[20]  P. Ridker,et al.  Endogenous tissue-type plasminogen activator and risk of myocardial infarction , 1993, The Lancet.

[21]  A. Yeung,et al.  The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. , 1995, The New England journal of medicine.

[22]  Y. Koga,et al.  Soluble form of P-selectin in patients with acute myocardial infarction. , 1994, Coronary artery disease.

[23]  A. Broillet,et al.  Assessment of myocardial perfusion by intermittent harmonic power Doppler using SonoVue, a new ultrasound contrast agent. , 1998, Investigative radiology.

[24]  R. Brandes,et al.  Supplementation of hypercholesterolaemic rabbits with L-arginine reduces the vascular release of superoxide anions and restores NO production. , 1995, Atherosclerosis.

[25]  T. Lüscher,et al.  Oxidized low density lipoproteins induce mRNA expression and release of endothelin from human and porcine endothelium. , 1992, Circulation research.

[26]  A. Gearing,et al.  Soluble forms of E-selectin, ICAM-1 and VCAM-1 are present in the supernatants of cytokine activated cultured endothelial cells. , 1992, Biochemical and biophysical research communications.

[27]  P. Ridker,et al.  Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men , 1998, The Lancet.

[28]  C. Dollery,et al.  Role of endothelium in the maintenance of low pulmonary vascular tone in normal children. , 1994, Circulation.

[29]  Jiang Li,et al.  Non-invasive detection of endothelial dysfunction in patients with essential hypertension. , 1997, International journal of cardiology.

[30]  D. Glogar,et al.  Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. , 1997, Atherosclerosis.

[31]  A. Yeung,et al.  Close relation of endothelial function in the human coronary and peripheral circulations. , 1995, Journal of the American College of Cardiology.

[32]  P. Declerck,et al.  Correlations between t-PA and PAI-1 antigen and activity and t-PA/PAI-1 complexes in plasma of control subjects and of patients with increased t-PA or PAI-1 levels. , 1990, Thrombosis research.

[33]  K. Usadel,et al.  Elevated endothelin-1 levels after cigarette smoking. , 1994, Metabolism: clinical and experimental.

[34]  J. Hodgson,et al.  Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. , 1994, Journal of the American College of Cardiology.

[35]  J. Viikari,et al.  Influence of cardiovascular risk status on coronary flow reserve in healthy young men. , 1997, The American journal of cardiology.

[36]  S. Bode-Böger,et al.  Elevated L-arginine/dimethylarginine ratio contributes to enhanced systemic NO production by dietary L-arginine in hypercholesterolemic rabbits. , 1996, Biochemical and biophysical research communications.

[37]  T. Lehtimäki,et al.  In vivo low density lipoprotein oxidation relates to coronary reactivity in young men. , 1997, Journal of the American College of Cardiology.

[38]  T. Lehtimäki,et al.  Coronary Flow Reserve Is Reduced in Young Men With IDDM , 1998, Diabetes.

[39]  J. Manson,et al.  Prospective study of endogenous tissue plasminogen activator and risk of stroke , 1994, The Lancet.

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

[41]  K. Williams,et al.  Atherosclerosis--an inflammatory disease. , 1999, The New England journal of medicine.

[42]  H. Drexler,et al.  Endothelial Function in Human Coronary Arteries In Vivo: Focus on Hypercholesterolemia , 1991, Hypertension.

[43]  P. Vallance,et al.  Biological significance of endogenous methylarginines that inhibit nitric oxide synthases. , 1999, Cardiovascular research.

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

[45]  J. Jansson,et al.  von Willebrand factor in plasma: a novel risk factor for recurrent myocardial infarction and death , 1992, British heart journal.

[46]  S. Higano,et al.  Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. , 2000, Circulation.

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

[48]  P. Vanhoutte Endothelium and Control of Vascular Function State of the Art Lecture , 1989, Hypertension.

[49]  A. Henderson,et al.  St Cyres lecture. Endothelium in control. , 1991, British heart journal.

[50]  J. Deanfield,et al.  Smooth muscle dysfunction occurs independently of impaired endothelium-dependent dilation in adults at risk of atherosclerosis. , 1998, Journal of the American College of Cardiology.

[51]  B. F. Becker,et al.  Different endothelial mechanisms involved in coronary responses to known vasodilators. , 1992, The American journal of physiology.

[52]  J. Deanfield,et al.  Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults. , 1996, The New England journal of medicine.

[53]  T Akasaka,et al.  Noninvasive assessment of significant left anterior descending coronary artery stenosis by coronary flow velocity reserve with transthoracic color Doppler echocardiography. , 1998, Circulation.

[54]  P. Tsao,et al.  Is NO an endogenous antiatherogenic molecule? , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[55]  S. Thompson,et al.  Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. , 1995, The New England journal of medicine.

[56]  M. Bell,et al.  Endothelin in coronary endothelial dysfunction and early atherosclerosis in humans. , 1995, Circulation.

[57]  D. Steinberg,et al.  Lipoproteins and the pathogenesis of atherosclerosis. , 1987, Circulation.

[58]  W E Haefeli,et al.  Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. , 1995, Circulation.

[59]  S. Moncada,et al.  EFFECTS OF ENDOTHELIUM-DERIVED NITRIC OXIDE ON PERIPHERAL ARTERIOLAR TONE IN MAN , 1989, The Lancet.

[60]  P. Groop,et al.  Chronic hyperglycemia impairs endothelial function and insulin sensitivity via different mechanisms in insulin-dependent diabetes mellitus. , 1996, Circulation.

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

[62]  P. Vanhoutte,et al.  Flow-induced release of endothelium-derived relaxing factor. , 1986, The American journal of physiology.

[63]  G. Rubanyi,et al.  The role of endothelium in cardiovascular homeostasis and diseases. , 1993, Journal of cardiovascular pharmacology.

[64]  A. Yeung,et al.  Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. , 1990, Circulation.

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

[66]  P. Libby,et al.  An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[67]  S. Bode-Böger,et al.  Quantification of nitrite and nitrate in human urine and plasma as pentafluorobenzyl derivatives by gas chromatography-mass spectrometry using their 15N-labelled analogs. , 1994, Journal of chromatography. B, Biomedical applications.

[68]  P. Mannucci,et al.  von Willebrand factor: a marker of endothelial damage? , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[69]  P. Tsao,et al.  Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. , 1998, Circulation.

[70]  J. Whitworth,et al.  EFFECTS OF DIET ON MEASUREMENT OF NITRIC OXIDE METABOLITES , 1997, Clinical and experimental pharmacology & physiology.

[71]  P. Marraccini,et al.  Plasma cholesterol regulates soluble cell adhesion molecule expression in familial hypercholesterolemia. , 1997, Circulation.

[72]  A. Blann,et al.  Circulating Endothelial Cell/Leukocyte Adhesion Molecules in Atherosclerosis , 1994, Thrombosis and Haemostasis.

[73]  N. Alpert,et al.  Effects of short-term treatment of hyperlipidemia on coronary vasodilator function and myocardial perfusion in regions having substantial impairment of baseline dilator reverse. , 1998, Circulation.

[74]  N. Kokolis,et al.  Fatty streaks and fibrous plaques in human aorta show increased plasminogen activator activity. , 1988, Haemostasis.

[75]  D. Celermajer,et al.  Cigarette Smoking Is Associated With Dose‐Related and Potentially Reversible Impairment of Endothelium‐Dependent Dilation in Healthy Young Adults , 1993, Circulation.

[76]  O. Raitakari,et al.  Effect of Lp(a) on the early functional and structural changes of atherosclerosis. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[77]  H. Crijns,et al.  Reduction of transient myocardial ischemia with pravastatin in addition to the conventional treatment in patients with angina pectoris. REGRESS Study Group. , 1996, Circulation.

[78]  P. Ganz,et al.  Effect of cholesterol reduction on myocardial ischemia in patients with coronary disease. , 1997, Circulation.

[79]  M. Cybulsky,et al.  Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. , 1992, The Journal of clinical investigation.

[80]  A. Gotto,et al.  Levels of soluble cell adhesion molecules in patients with dyslipidemia. , 1996, Circulation.

[81]  S. Moncada EIGHTH GADDUM MEMORIAL LECTURE UNIVERSITY OF LONDON INSTITUTE OF EDUCATION DECEMBER 1980: BIOLOGICAL IMPORTANCE OF PROSTACYCLIN , 1982, British journal of pharmacology.

[82]  K. Okumura,et al.  Soluble P-selectin is released into the coronary circulation after coronary spasm. , 1995, Circulation.

[83]  L. Viinikka,et al.  Nitric oxide as a challenge for the clinical chemistry laboratory. , 1996, Scandinavian journal of clinical and laboratory investigation.

[84]  M. Phelps,et al.  Effect of short-term cardiovascular conditioning and low-fat diet on myocardial blood flow and flow reserve. , 1995, Circulation.

[85]  D. Webb,et al.  The pharmacology of human blood vessels in vivo. , 1995, Journal of vascular research.

[86]  R. Ross The pathogenesis of atherosclerosis: a perspective for the 1990s , 1993, Nature.

[87]  E. Nabel,et al.  Large coronary arteries in humans are responsive to changing blood flow: an endothelium-dependent mechanism that fails in patients with atherosclerosis. , 1990, Journal of the American College of Cardiology.

[88]  Stanley Azen,et al.  Coronary Angiographic Changes with Lovastatin Therapy: The Monitored Atherosclerosis Regression Study (MARS) , 1993, Annals of Internal Medicine.

[89]  S. Schwartz,et al.  A technique to investigate surface morphology and endothelial cell replication of small arteries: a study in acute angiotensin-induced hypertensive rats. , 1982, Microvascular research.

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

[91]  R. Schmieder,et al.  Increased bioavailability of nitric oxide after lipid-lowering therapy in hypercholesterolemic patients: a randomized, placebo-controlled, double-blind study. , 1998, Circulation.

[92]  R. Braman,et al.  Nanogram nitrite and nitrate determination in environmental and biological materials by vanadium (III) reduction with chemiluminescence detection. , 1989, Analytical chemistry.

[93]  Simon C Watkins,et al.  Microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells. , 1998, Circulation.

[94]  P. Ganz,et al.  Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. , 1986, The New England journal of medicine.

[95]  E. Boerwinkle,et al.  Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atherosclerosis Risk In Communities (ARIC) study. , 1997, Circulation.

[96]  J. Neefjes,et al.  E-selectin and intercellular adhesion molecule-1 are released by activated human endothelial cells in vitro. , 1992, Immunology.

[97]  M. Omata,et al.  Reduced coronary flow reserve in hypercholesterolemic patients without overt coronary stenosis. , 1996, Circulation.

[98]  M. Underwood,et al.  Increased fibrinolytic activity in the intima of atheromatous coronary arteries: protection at a price. , 1993, Cardiovascular research.

[99]  M. Lewis,et al.  Endothelium‐derived relaxing factor alters calcium fluxes in rabbit aorta: a cyclic guanosine monophosphate‐mediated effect. , 1986, The Journal of physiology.

[100]  A M Zeiher,et al.  Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. , 2000, Circulation.

[101]  L. Tavazzi,et al.  The PLAT Study: hemostatic function in relation to atherothrombotic ischemic events in vascular disease patients. Principal results. PLAT Study Group. Progetto Lombardo Atero-Trombosi (PLAT) Study Group. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[102]  T. Ueno,et al.  Increased soluble form of P-selectin in patients with unstable angina. , 1995, Circulation.

[103]  J. Viikari,et al.  Early impairment of coronary flow reserve in young men with borderline hypertension. , 1998, Journal of the American College of Cardiology.

[104]  S. Iacobelli,et al.  Increased levels of soluble P-selectin in hypercholesterolemic patients. , 1998, Circulation.

[105]  S. Lundin,et al.  Metabolism and excretion of nitric oxide in humans. An experimental and clinical study. , 1993, Circulation research.

[106]  P. Tsao,et al.  Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. , 1999, Circulation.

[107]  P. López-Jaramillo,et al.  The L-arginine: nitric oxide pathway. , 1993, Current opinion in nephrology and hypertension.

[108]  S. Moore Thromboatherosclerosis in normolipemic rabbits. A result of continued endothelial damage. , 1973, Laboratory investigation; a journal of technical methods and pathology.

[109]  D. Spiegelhalter,et al.  Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. , 1994, Journal of the American College of Cardiology.

[110]  L. Ignarro Biosynthesis and metabolism of endothelium-derived nitric oxide. , 1990, Annual review of pharmacology and toxicology.

[111]  J. Cooke,et al.  Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. , 1999, Circulation.

[112]  A. Zeiher,et al.  Impaired endothelium-dependent vasodilation of coronary resistance vessels is associated with exercise-induced myocardial ischemia. , 1995, Circulation.

[113]  D. Harrison,et al.  Hypercholesterolemia increases endothelial superoxide anion production. , 1993, The Journal of clinical investigation.

[114]  K. Huber,et al.  Concentration of endogenous tPA antigen in coronary artery disease: relation to thrombotic events, aspirin treatment, hyperlipidemia, and multivessel disease. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[115]  J. Loscalzo,et al.  Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans. , 1990, The Journal of clinical investigation.

[116]  W. Mayhan Endothelium-dependent responses of cerebral arterioles to adenosine 5'-diphosphate. , 1992, Journal of vascular research.

[117]  C. Lang,et al.  Regulation of local tissue-type plasminogen activator release by endothelium-dependent and endothelium-independent agonists in human vasculature. , 1998, Journal of the American College of Cardiology.

[118]  O. Raitakari,et al.  Arterial Endothelial Dysfunction Related to Passive Smoking Is Potentially Reversible in Healthy Young Adults , 1999, Annals of Internal Medicine.