Clinical Science Review Article: Understanding the Implications of Diabetes on the Vascular System

Patients with diabetes comprise an extremely complex subset of patients for the vascular surgeon. Often, they have numerous comorbidities that can further complicate matters. The diabetic environment is highly complex and the interplay of various diseases makes this an extremely challenging condition to manage. Knowing the mechanisms by which diabetes inflicts adverse microscopic changes in the vasculature allows the clinician to anticipate problems and minimize the heightened risks observed in diabetic patients undergoing surgery. In this review, we will illustrate how diabetes affects the vasculature and how the molecular and cellular derangements that occur in diabetic environments lead to these pathophysiologic consequences.

[1]  M. Kibbe,et al.  Insulin enhances the effect of nitric oxide at inhibiting neointimal hyperplasia in a rat model of type 1 diabetes. , 2010, American journal of physiology. Heart and circulatory physiology.

[2]  P. Blankestijn,et al.  Progenitor cells and vascular function are impaired in patients with chronic kidney disease. , 2010, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[3]  E. Falk,et al.  Circulating Endothelial Progenitor Cells Do Not Contribute to Plaque Endothelium in Murine Atherosclerosis , 2010, Circulation.

[4]  A. Avogaro,et al.  Endothelial progenitors in pulmonary hypertension: new pathophysiology and therapeutic implications , 2010, European Respiratory Journal.

[5]  Yizhi Liu,et al.  Endothelial progenitor cells (EPCs) mobilized and activated by neurotrophic factors may contribute to pathologic neovascularization in diabetic retinopathy. , 2010, The American journal of pathology.

[6]  B. Lévy,et al.  Circulating progenitor cells and cardiovascular outcomes: latest evidence on angiotensin-converting enzyme inhibitors , 2009 .

[7]  Biao Xu,et al.  Advanced glycation end products impair function of late endothelial progenitor cells through effects on protein kinase Akt and cyclooxygenase-2. , 2009, Biochemical and biophysical research communications.

[8]  E. Halm,et al.  Risk Factors for Perioperative Death and Stroke After Carotid Endarterectomy: Results of the New York Carotid Artery Surgery Study , 2009, Stroke.

[9]  G. Moneta Association between minor and major surgical complications after carotid endarterectomy: Results of the New York Carotid Artery Surgery study , 2009 .

[10]  W. Nauseef Biological Roles for the NOX Family NADPH Oxidases* , 2008, Journal of Biological Chemistry.

[11]  M. Anand-Srivastava,et al.  Role of oxidative stress in high glucose-induced decreased expression of Gialpha proteins and adenylyl cyclase signaling in vascular smooth muscle cells. , 2008, American journal of physiology. Heart and circulatory physiology.

[12]  G. Spinetti,et al.  Diabetes and vessel wall remodelling: from mechanistic insights to regenerative therapies. , 2008, Cardiovascular research.

[13]  A. Avogaro,et al.  Oxidative stress and vascular disease in diabetes: is the dichotomization of insulin signaling still valid? , 2008, Free radical biology & medicine.

[14]  A. Pandolfi,et al.  Chronic hyperglicemia and nitric oxide bioavailability play a pivotal role in pro-atherogenic vascular modifications , 2007, Genes & Nutrition.

[15]  A. Avogaro,et al.  Glucose tolerance is negatively associated with circulating progenitor cell levels , 2007, Diabetologia.

[16]  Po-Len Liu,et al.  High Glucose Impairs Early and Late Endothelial Progenitor Cells by Modifying Nitric Oxide–Related but Not Oxidative Stress–Mediated Mechanisms , 2007, Diabetes.

[17]  P. Galuppo,et al.  Endothelial Nitric Oxide Synthase Uncoupling Impairs Endothelial Progenitor Cell Mobilization and Function in Diabetes , 2007, Diabetes.

[18]  A. Avogaro,et al.  Number and Function of Endothelial Progenitor Cells as a Marker of Severity for Diabetic Vasculopathy , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[19]  G. Hart,et al.  Cell signaling, the essential role of O-GlcNAc! , 2006, Biochimica et biophysica acta.

[20]  E. Edelman,et al.  Vascular Neointimal Formation and Signaling Pathway Activation in Response to Stent Injury in Insulin-Resistant and Diabetic Animals , 2005, Circulation research.

[21]  B. H. Shah,et al.  Agonist-Induced Interactions between Angiotensin AT1 and Epidermal Growth Factor Receptors , 2005, Molecular Pharmacology.

[22]  S. Fichtlscherer,et al.  Reduced Number of Circulating Endothelial Progenitor Cells Predicts Future Cardiovascular Events: Proof of Concept for the Clinical Importance of Endogenous Vascular Repair , 2005, Circulation.

[23]  Michael Brownlee,et al.  The pathobiology of diabetic complications: a unifying mechanism. , 2005, Diabetes.

[24]  A. Avogaro,et al.  Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. , 2005, Journal of the American College of Cardiology.

[25]  StephanGielen,et al.  Hyperglycemia Reduces Survival and Impairs Function of Circulating Blood-Derived Progenitor Cells , 2005 .

[26]  A. Zeiher,et al.  p38 Mitogen-Activated Protein Kinase Downregulates Endothelial Progenitor Cells , 2005, Circulation.

[27]  G. King,et al.  Proatherosclerotic Mechanisms Involving Protein Kinase C in Diabetes and Insulin Resistance , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[28]  K. Todd,et al.  Endothelial Progenitor Cells During Cerebrovascular Disease , 2005, Stroke.

[29]  J. Kinoshita Mechanisms initiating cataract formation , 2005 .

[30]  D. Mcmaster,et al.  High glucose mediates pro‐oxidant and antioxidant enzyme activities in coronary endothelial cells , 2004, Diabetes, obesity & metabolism.

[31]  Eun-Seok Jeon,et al.  Decreased Number and Impaired Angiogenic Function of Endothelial Progenitor Cells in Patients With Chronic Renal Failure , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[32]  M. Birnbaum,et al.  Protein Kinase C θ Inhibits Insulin Signaling by Phosphorylating IRS1 at Ser1101* , 2004, Journal of Biological Chemistry.

[33]  C. Hedrick,et al.  Hyperglycaemia-induced superoxide production decreases eNOS expression via AP-1 activation in aortic endothelial cells , 2004, Diabetologia.

[34]  M. Tuck,et al.  Insulin stimulates endogenous angiotensin II production via a mitogen-activated protein kinase pathway in vascular smooth muscle cells , 2004, Journal of hypertension.

[35]  S. Dimmeler,et al.  Endothelial Progenitor Cells: Characterization and Role in Vascular Biology , 2004, Circulation research.

[36]  N. Alp,et al.  Regulation of Endothelial Nitric Oxide Synthase by Tetrahydrobiopterin in Vascular Disease , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[37]  B. Davis,et al.  Outcomes in Patients With Diabetes Mellitus Undergoing Percutaneous Coronary Intervention in the Current Era: A Report From the Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) Trial , 2004, Circulation.

[38]  H. Ditschuneit,et al.  Effect of insulin on growth of cultured human arterial smooth muscle cells , 1981, Diabetologia.

[39]  Frank J T Staal,et al.  Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. , 2004, Diabetes.

[40]  K. Griendling,et al.  Reactive oxygen species in the vasculature: molecular and cellular mechanisms. , 2003, Hypertension.

[41]  L. Rossetti,et al.  Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. , 2003, The Journal of clinical investigation.

[42]  D. Harrison,et al.  Interactions of Peroxynitrite, Tetrahydrobiopterin, Ascorbic Acid, and Thiols , 2003, Journal of Biological Chemistry.

[43]  O. Carretero,et al.  Novel NAD(P)H Oxidase Inhibitor Suppresses Angioplasty-Induced Superoxide and Neointimal Hyperplasia of Rat Carotid Artery , 2003, Circulation research.

[44]  M. Mifune,et al.  Insulin-Induced Akt Activation Is Inhibited by Angiotensin II in the Vasculature Through Protein Kinase C-&agr; , 2003, Hypertension.

[45]  P. Tsao,et al.  Impaired Nitric Oxide Synthase Pathway in Diabetes Mellitus: Role of Asymmetric Dimethylarginine and Dimethylarginine Dimethylaminohydrolase , 2002, Circulation.

[46]  Peter Libby,et al.  Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. , 2002, JAMA.

[47]  R. Hayward,et al.  Perioperative cardiovascular risk stratification of patients with diabetes who undergo elective major vascular surgery. , 2002, Journal of vascular surgery.

[48]  M. White,et al.  Phosphorylation of Ser307 in Insulin Receptor Substrate-1 Blocks Interactions with the Insulin Receptor and Inhibits Insulin Action* , 2002, The Journal of Biological Chemistry.

[49]  F. Logerfo,et al.  Is Diabetes a Risk Factor for Patients Undergoing Open Abdominal Aortic Aneurysm Repair? , 2002, Vascular and endovascular surgery.

[50]  D. Alessi,et al.  Phosphoinositide-regulated kinases and phosphoinositide phosphatases. , 2001, Chemical reviews.

[51]  C. Indolfi,et al.  Effects of Balloon Injury on Neointimal Hyperplasia in Streptozotocin-Induced Diabetes and in Hyperinsulinemic Nondiabetic Pancreatic Islet–Transplanted Rats , 2001, Circulation.

[52]  E. Martelli,et al.  Carotid endarterectomy in diabetic patients. , 2001, Journal of vascular surgery.

[53]  G. King,et al.  Endothelial dysfunction in diabetes mellitus: role in cardiovascular disease. , 2001, Heart failure monitor.

[54]  G. Reaven,et al.  Hyperinsulinemia: the missing link among oxidative stress and age-related diseases? , 2000, Free radical biology & medicine.

[55]  J. Herlitz,et al.  Mortality, mode of death and risk indicators for death during 5 years after coronary artery bypass grafting among patients with and without a history of diabetes mellitus , 2000, Coronary artery disease.

[56]  E. Nishida,et al.  Two co‐existing mechanisms for nuclear import of MAP kinase: passive diffusion of a monomer and active transport of a dimer , 1999, The EMBO journal.

[57]  A. Kashiwagi,et al.  Free radical production in endothelial cells as a pathogenetic factor for vascular dysfunction in the insulin resistance state. , 1999, Diabetes research and clinical practice.

[58]  V. Hachinski,et al.  The North American Symptomatic Carotid Endarterectomy Trial : surgical results in 1415 patients. , 1999, Stroke.

[59]  L. Norgren,et al.  Diabetes mellitus as a risk factor for early outcome after carotid endarterectomy--a population-based study. , 1999, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

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

[61]  W. Sessa,et al.  Regulation of endothelium-derived nitric oxide production by the protein kinase Akt , 1999, Nature.

[62]  J. Cazenave,et al.  The kinetics of translocation and cellular quantity of protein kinase C in human leukocytes are modified during spaceflight , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

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

[64]  A. Lee,et al.  Contributions of polyol pathway to oxidative stress in diabetic cataract , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[65]  M. Hadamitzky,et al.  Diabetes mellitus and the clinical and angiographic outcome after coronary stent placement. , 1998, Journal of the American College of Cardiology.

[66]  A. Schmidt,et al.  Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts , 1998, Nature Medicine.

[67]  A. Brunet,et al.  Growth Factor–induced p42/p44 MAPK Nuclear Translocation and Retention Requires Both MAPK Activation and Neosynthesis of Nuclear Anchoring Proteins , 1998, The Journal of cell biology.

[68]  E. Goldsmith,et al.  Phosphorylation of the MAP Kinase ERK2 Promotes Its Homodimerization and Nuclear Translocation , 1998, Cell.

[69]  L. Graves,et al.  Angiotensin II stimulates ERK via two pathways in epithelial cells: protein kinase C suppresses a G–protein coupled receptor–EGF receptor transactivation pathway , 1998, The EMBO journal.

[70]  N. Risler,et al.  Proliferative effect of insulin on cultured smooth muscle cells from rat mesenteric resistance vessels. , 1998, American journal of hypertension.

[71]  C. Kahn,et al.  Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels. A potential role for serine phosphorylation in insulin/angiotensin II crosstalk. , 1997, The Journal of clinical investigation.

[72]  T. Billiar,et al.  Adenoviral transfer of the inducible nitric oxide synthase gene blocks endothelial cell apoptosis. , 1997, Surgery.

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

[74]  Takayuki Asahara,et al.  Isolation of Putative Progenitor Endothelial Cells for Angiogenesis , 1997, Science.

[75]  T. Hohman,et al.  Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats , 1997, Diabetologia.

[76]  D. Faxon,et al.  Coronary angioplasty in diabetic patients. The National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry. , 1996, Circulation.

[77]  P. Parker,et al.  p42 MAPK phosphorylates 80 kDa MARCKS at Ser‐113 , 1996, FEBS letters.

[78]  M. Horiuchi,et al.  Vasoactive substances regulate vascular smooth muscle cell apoptosis. Countervailing influences of nitric oxide and angiotensin II. , 1996, Circulation research.

[79]  M. Quon,et al.  Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells. , 1996, The Journal of clinical investigation.

[80]  A. M. Lefer,et al.  Mechanisms of vascular preservation by a novel NO donor following rat carotid artery intimal injury. , 1995, The American journal of physiology.

[81]  G. Condorelli,et al.  Inhibition of cellular ras prevents smooth muscle cell proliferation after vascular injury in vivo , 1995, Nature Medicine.

[82]  N. Jones,et al.  ATF‐2 contains a phosphorylation‐dependent transcriptional activation domain. , 1995, The EMBO journal.

[83]  Sookja K. Chung,et al.  Demonstration that polyol accumulation is responsible for diabetic cataract by the use of transgenic mice expressing the aldose reductase gene in the lens. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[84]  M. Weber,et al.  RAS and RAF-1 form a signalling complex with MEK-1 but not MEK-2 , 1994, Molecular and cellular biology.

[85]  S Amerini,et al.  Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. , 1994, The Journal of clinical investigation.

[86]  M. Karin,et al.  c-Jun N-terminal phosphorylation correlates with activation of the JNK subgroup but not the ERK subgroup of mitogen-activated protein kinases , 1994, Molecular and cellular biology.

[87]  N. Fineberg,et al.  Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. , 1994, The Journal of clinical investigation.

[88]  R. Bucala,et al.  Immunohistochemical localization of advanced glycosylation end products in coronary atheroma and cardiac tissue in diabetes mellitus. , 1993, The American journal of pathology.

[89]  C. Crews,et al.  Raf-1 forms a stable complex with Mek1 and activates Mek1 by serine phosphorylation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[90]  R. Davis,et al.  Serum-induced translocation of mitogen-activated protein kinase to the cell surface ruffling membrane and the nucleus , 1993, The Journal of cell biology.

[91]  S. Elledge,et al.  Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 , 1993, Nature.

[92]  Jonathan A. Cooper,et al.  Mammalian Ras interacts directly with the serine/threonine kinase raf , 1993, Cell.

[93]  T. Roberts,et al.  Raf-1 and p21v-ras cooperate in the activation of mitogen-activated protein kinase. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[94]  M. Weber,et al.  Complexes of Ras.GTP with Raf-1 and mitogen-activated protein kinase kinase. , 1993, Science.

[95]  C. Lange-Carter,et al.  A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf , 1993, Science.

[96]  C. Molloy,et al.  Angiotensin II stimulation of rapid protein tyrosine phosphorylation and protein kinase activation in rat aortic smooth muscle cells. , 1993, The Journal of biological chemistry.

[97]  B. Margolis,et al.  Phosphatidylinositol 3′‐kinase is activated by association with IRS‐1 during insulin stimulation. , 1992, The EMBO journal.

[98]  C. Kahn,et al.  Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein , 1991, Nature.

[99]  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.

[100]  C. Nathan,et al.  Reduced biopterin as a cofactor in the generation of nitrogen oxides by murine macrophages. , 1989, The Journal of biological chemistry.

[101]  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.

[102]  A. Cerami,et al.  Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. , 1988, The New England journal of medicine.

[103]  S Moncada,et al.  The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. , 1987, Biochemical and biophysical research communications.

[104]  S. Moncada,et al.  Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor , 1987, Nature.

[105]  G. Bondjers,et al.  Regional Accumulations of T Cells, Macrophages, and Smooth Muscle Cells in the Human Atherosclerotic Plaque , 1986, Arteriosclerosis.

[106]  C. Kahn,et al.  Insulin rapidly stimulates tyrosine phosphorylation of a Mr-185,000 protein in intact cells , 1985, Nature.

[107]  R. Aiyer Structural characterization of insulin receptors. I. Hydrodynamic properties of receptors from turkey erythrocytes. , 1983, The Journal of biological chemistry.

[108]  R. Aiyer Structural characterization of insulin receptors. II. Subunit composition of receptors from turkey erythrocytes. , 1983, The Journal of biological chemistry.

[109]  A. Meister Selective modification of glutathione metabolism. , 1983, Science.

[110]  J. Halter,et al.  Aldose reductase inhibition improves nerve conduction velocity in diabetic patients. , 1983, The New England journal of medicine.

[111]  C. Kahn,et al.  Insulin stimulates tyrosine phosphorylation of the insulin receptor in a cell-free system , 1982, Nature.

[112]  S D Varma,et al.  Implications of aldose reductase in cataracts in human diabetes. , 1979, Investigative ophthalmology & visual science.

[113]  J. Kinoshita Mechanisms initiating cataract formation. Proctor Lecture. , 1974, Investigative ophthalmology.

[114]  H. Hers Le mécanisme de la transformation de glucose en fructose par les vésicules séminales , 1956 .

[115]  H. Hers [The mechanism of the transformation of glucose in fructose in the seminal vesicles]. , 1956, Biochimica et biophysica acta.