Regulatory Effects of O-GlcNAcylation in Vascular Smooth Muscle Cells on Diabetic Vasculopathy
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Vascular complications from uncontrolled hyperglycemia are the leading cause of death in patients with diabetes mellitus. Previous reports have shown a strong correlation between hyperglycemia and vascular calcification, which increases mortality and morbidity in individuals with diabetes. However, the precise underlying molecular mechanisms of hyperglycemia-induced vascular calcification remain largely unknown. Transdifferentiation of vascular smooth muscle cells (VSMC) into osteoblast-like cells is a known culprit underlying the development of vascular calcification in the diabetic vasculature. Pathological conditions such as high glucose levels and oxidative stress are linked to enhanced osteogenic differentiation of VSMC both in vivo and in vitro. It has been demonstrated that increased expression of runt-related transcription factor 2 (Runx2), a bone-related transcription factor, in VSMC is necessary and sufficient for the induction of VSMC calcification. Addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) moiety to the serine/threonine residues of target proteins (O-GlcNAcylation) has been observed in the arteries of diabetic patients, as well as in animal models in association with the enhanced expression of Runx2 and aggravated vascular calcification. O-GlcNAcylation is a dynamic and tightly regulated process, that is mediated by 2 enzymes, O-GlcNAc transferase and O-GlcNAcase. Glucose is metabolized into UDP-β-D-N-acetylglucosamine, an active sugar donor of O-GlcNAcylation via the hexosamine biosynthetic pathway. Overall increases in the O-GlcNAcylation of cellular proteins have been closely associated with cardiovascular complications of diabetes. In this review, the authors provide molecular insights into cardiovascular complications, including diabetic vasculopathy, that feature increased O-GlcNAcylation in people with diabetes.
Abstract
Vascular complications from uncontrolled hyperglycemia are the leading cause of death in patients with diabetes mellitus. Previous reports have shown a strong correlation between hyperglycemia and vascular calcification, which increases mortality and morbidity in individuals with diabetes. However, the precise underlying molecular mechanisms of hyperglycemia-induced vascular calcification remain largely unknown. Transdifferentiation of vascular smooth muscle cells (VSMC) into osteoblast-like cells is a known culprit underlying the development of vascular calcification in the diabetic vasculature. Pathological conditions such as high glucose levels and oxidative stress are linked to enhanced osteogenic differentiation of VSMC both in vivo and in vitro. It has been demonstrated that increased expression of runt-related transcription factor 2 (Runx2), a bone-related transcription factor, in VSMC is necessary and sufficient for the induction of VSMC calcification. Addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) moiety to the serine/threonine residues of target proteins (O-GlcNAcylation) has been observed in the arteries of diabetic patients, as well as in animal models in association with the enhanced expression of Runx2 and aggravated vascular calcification. O-GlcNAcylation is a dynamic and tightly regulated process, that is mediated by 2 enzymes, O-GlcNAc transferase and O-GlcNAcase. Glucose is metabolized into UDP-β-D-N-acetylglucosamine, an active sugar donor of O-GlcNAcylation via the hexosamine biosynthetic pathway. Overall increases in the O-GlcNAcylation of cellular proteins have been closely associated with cardiovascular complications of diabetes. In this review, the authors provide molecular insights into cardiovascular complications, including diabetic vasculopathy, that feature increased O-GlcNAcylation in people with diabetes.
참고문헌 (81)
- International Diabetes Federation, "IDF diabetes atlas" (2019), International Diabetes Federation
- Badimon L, "Thrombosis formation on atherosclerotic lesions and plaque rupture", J Intern Med, 276, pp.618~632 (2014)
- Lacolley P, "Vascular smooth muscle cells and arterial stiffening : relevance in development, aging, and disease", Physiol Rev, 97, pp.1555~1617 (2017)
- Boström KI, "The regulation of valvular and vascular sclerosis by osteogenic morphogens", Circ Res, 109, pp.564~577 (2011)
- Chen NX, "Arterial calcification in diabetes", Curr Diab Rep, 3, pp.28~32 (2003)
- Carr JJ, "Calcified atherosclerotic plaque and bone mineral density in type 2 diabetes : the diabetes heart study", Bone, 42, pp.43~52 (2008)
- Boström KI, "Activation of vascular bone morphogenetic protein signaling in diabetes mellitus", Circ Res, 108, pp.446~457 (2011)
- Federici M, "Insulin-dependent activation of endothelial nitric oxide synthase is impaired by O-linked glycosylation modification of signaling proteins in human coronary endothelial cells", Circulation, 106, pp.466~472 (2002)
- Bennett CE, "Exercise training mitigates aberrant cardiac protein O-GlcNAcylation in streptozotocin-induced diabetic mice", Life Sci, 92, pp.657~663 (2013)
- Heath JM, "Activation of AKT by O-linked N-acetylglucosamine induces vascular calcification in diabetes mellitus", Circ Res, 114, pp.1094~1102 (2014)
- Wang J, "A nutrient-sensing pathway regulates leptin gene expression in muscle and fat", Nature, 393, pp.684~688 (1998)
- Lunde IG, "Cardiac O-GlcNAc signaling is increased in hypertrophy and heart failure", Physiol Genomics, 44, pp.162~172 (2012)
- Watson LJ, "O-linked β-N-acetylglucosamine transferase is indispensable in the failing heart", Proc Natl Acad Sci U S A, 107, pp.17797~17802 (2010)
- Laczy B, "Inhibition of O-GlcNAcase in perfused rat hearts by NAG-thiazolines at the time of reperfusion is cardioprotective in an O-GlcNAc-dependent manner", Am J Physiol Heart Circ Physiol, 299, pp.H1715~H1727 (2010)
- Ngoh GA, "Augmented O-GlcNAc signaling attenuates oxidative stress and calcium overload in cardiomyocytes", Amino Acids, 40, pp.895~911 (2011)
- Jones SP, "Cardioprotection by N-acetylglucosamine linkage to cellular proteins", Circulation, 117, pp.1172~1182 (2008)
- Darley-Usmar VM, "Protein O-linked β-N-acetylglucosamine : a novel effector of cardiomyocyte metabolism and function", J Mol Cell Cardiol, 52, pp.538~549 (2012)
- Champattanachai V, "Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein O-GlcNAc and increased mitochondrial Bcl-2", Am J Physiol Cell Physiol, 294, pp.C1509~C1520 (2008)
- Ma J, "Protein O-GlcNAcylation in diabetes and diabetic complications", Expert Rev Proteomics, 10, pp.365~380 (2013)
- Park Y, "Vascular dysfunction in type 2 diabetes : emerging targets for therapy", Expert Rev Cardiovasc Ther, 7, pp.209~213 (2009)
- Medford HM, "Chronic ingestion of a Western diet increases O-linked-β-N-acetylglucosamine(O-GlcNAc)protein modification in the rat heart", Life Sci, 90, pp.883~888 (2012)
- Akimoto Y, "Elevation of the post-translational modification of proteins by O-linked N-acetylglucosamine leads to deterioration of the glucose-stimulated insulin secretion in the pancreas of diabetic Goto-Kakizaki rats", Glycobiology, 17, pp.127~140 (2007)
- Johnson JD, "Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome", Proc Natl Acad Sci U S A, 103, pp.19575~19580 (2006)
- Yang X, "Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance", Nature, 451, pp.964~969 (2008)
- Nesto RW, "Correlation between cardiovascular disease and diabetes mellitus : current concepts", Am J Med, 116(Suppl 5A), pp.11S~22S (2004)
- Félétou M, "Endothelial dysfunction : a multifaceted disorder(The Wiggers Award Lecture)", Am J Physiol Heart Circ Physiol, 291, pp.H985~H1002 (2006)
- Chen K, "Nitric oxide in the vasculature : where does it come from and where does it go?", A quantitative perspective. Antioxid Redox Signal, 10, pp.1185~1198 (2008)
- Joannides R, "Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo", Circulation, 91, pp.1314~1319 (1995)
- Tomiyama H, "Relationship between endothelial function and fibrinolysis in early hypertension", Hypertension, 31, pp.321~327 (1998)
- Adams MR, "L-arginine reduces human monocyte adhesion to vascular endothelium and endothelial expression of cell adhesion molecules", Circulation, 95, pp.662~668 (1997)
- Nedeljkovic ZS, "Mechanisms of oxidative stress and vascular dysfunction", Postgrad Med J, 79, pp.195~199 (2003)
- Bonetti PO, "Endothelial dysfunction : a marker of atherosclerotic risk", Arterioscler Thromb Vasc Biol, 23, pp.168~175 (2003)
- Sena CM, "Endothelial dysfunction-a major mediator of diabetic vascular disease", Biochim Biophys Acta, 1832, pp.2216~2231 (2013)
- Du XL, "Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site", J Clin Invest, 108, pp.1341~1348 (2001)
- Musicki B, "Inactivation of phosphorylated endothelial nitric oxide synthase(Ser-1177)by O-GlcNAc in diabetes-associated erectile dysfunction", Proc Natl Acad Sci U S A, 102, pp.11870~11875 (2005)
- Wheatcroft SB, "Pathophysiological implications of insulin resistance on vascular endothelial function", Diabet Med, 20, pp.255~268 (2003)
- Beleznai T, "Activation of hexosamine pathway impairs nitric oxide(NO)-dependent arteriolar dilations by increased protein O-GlcNAcylation", Vascul Pharmacol, 56, pp.115~121 (2012)
- da Costa RM, "Increased O-GlcNAcylation of endothelial nitric oxide synthase compromises the anti-contractile properties of perivascular adipose tissue in metabolic syndrome", Front Physiol, 9, pp.341~341 (2018)
- Roger VL, "Heart disease and stroke statistics--2012 update : a report from the American Heart Association", Circulation, 125, pp.e2~e220 (2012)
- Avogaro A, "Mechanisms of ectopic calcification : implications for diabetic vasculopathy", Cardiovasc Diagn Ther, 5, pp.343~352 (2015)
- Abedin M, "Vascular calcification : mechanisms and clinical ramifications", Arterioscler Thromb Vasc Biol, 24, pp.1161~1170 (2004)
- Virmani R, "Recent highlights of ATVB : calcification", Arterioscler Thromb Vasc Biol, 34, pp.1329~1332 (2014)
- Mackey RH, "Calcifications, arterial stiffness and atherosclerosis", Adv Cardiol, 44, pp.234~244 (2007)
- Lanzer P, "Medial vascular calcification revisited : review and perspectives", Eur Heart J, 35, pp.1515~1525 (2014)
- Juutilainen A, "Thoracoabdominal calcifications predict cardiovascular disease mortality in type 2 diabetic and nondiabetic subjects : 18-year follow-up study", Diabetes Care, 33, pp.583~585 (2010)
- Sethi S, "Aortic stiffness : pathophysiology, clinical implications, and approach to treatment", Integr Blood Press Control, 7, pp.29~34 (2014)
- Vlachopoulos C, "Prediction of cardiovascular events and all-cause mortality with arterial stiffness : a systematic review and meta-analysis", J Am Coll Cardiol, 55, pp.1318~1327 (2010)
- Tousoulis D, "Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease", Int J Cardiol, 167, pp.1924~1928 (2013)
- Gordin D, "Aspects of hyperglycemia contribution to arterial stiffness and cardiovascular complications in patients with type 1 diabetes", J Diabetes Sci Technol, 10, pp.1059~1064 (2016)
- Theilade S, "Arterial stiffness is associated with cardiovascular, renal, retinal, and autonomic disease in type 1 diabetes", Diabetes Care, 36, pp.715~721 (2013)
- Koyama T, "Global increase in O-linked N-acetylglucosamine modification promotes osteoblast differentiation", Exp Cell Res, 338, pp.194~202 (2015)
- Sun C, "Glucose regulates tissue-specific chondro-osteogenic differentiation of human cartilage endplate stem cells via O-GlcNAcylation of Sox9 and Runx2", Stem Cell Res Ther, 10, pp.357~ (2019)
- Kim SH, "O-GlcNAc modification modulates the expression of osteocalcin via OSE2 and Runx2", Biochem Biophys Res Commun, 362, pp.325~329 (2007)
- Kunjathoor VV, "Increased atherosclerosis in streptozotocin-induced diabetic mice", J Clin Invest, 97, pp.1767~1773 (1996)
- Gomez D, "Smooth muscle cell phenotypic switching in atherosclerosis", Cardiovasc Res, 95, pp.156~164 (2012)
- Mikhail N, "Platelets, growth factors, and vascular smooth-muscle cells in hypertension and diabetes", J Cardiovasc Pharmacol, 22(Suppl 6), pp.S64~S74 (1993)
- Wall VZ, "Arterial smooth muscle", Arterioscler Thromb Vasc Biol, 34, pp.2175~2179 (2014)
- Li SL, "Enhanced proatherogenic responses in macrophages and vascular smooth muscle cells derived from diabetic db", db mice, 2006, pp.55, 2611~2619
- Natarajan R, "Lipid inflammatory mediators in diabetic vascular disease", Arterioscler Thromb Vasc Biol, 24, pp.1542~1548 (2004)
- Meng L, "Diabetic conditions promote binding of monocytes to vascular smooth muscle cells and their subsequent differentiation", Am J Physiol Heart Circ Physiol, 298, pp.H736~H745 (2010)
- Maile LA, "Hyperglycemia alters the responsiveness of smooth muscle cells to insulin-like growth factor-I", Endocrinology, 148, pp.2435~2443 (2007)
- Doran AC, "Role of smooth muscle cells in the initiation and early progression of atherosclerosis", Arterioscler Thromb Vasc Biol, 28, pp.812~819 (2008)
- Rask-Madsen C, "Proatherosclerotic mechanisms involving protein kinase C in diabetes and insulin resistance", Arterioscler Thromb Vasc Biol, 25, pp.487~496 (2005)
- Akimoto Y, "Hyperglycemia and the O-GlcNAc transferase in rat aortic smooth muscle cells : elevated expression and altered patterns of O-GlcNAcylation", Arch Biochem Biophys, 389, pp.166~175 (2001)
- Vigetti D, "Role of UDP-N-acetylglucosamine(GlcNAc)and O-GlcNAcylation of hyaluronan synthase 2 in the control of chondroitin sulfate and hyaluronan synthesis", J Biol Chem, 287, pp.35544~35555 (2012)
- Moretto P, "Regulation of hyaluronan synthesis in vascular diseases and diabetes", J Diabetes Res, 2015, pp.167283~167283 (2015)
- Han I, "Reduced O glycosylation of Sp1 is associated with increased proteasome susceptibility", Mol Cell Biol, 17, pp.2550~2558 (1997)
- Faries PL, "Human vascular smooth muscle cells of diabetic origin exhibit increased proliferation, adhesion, and migration", J Vasc Surg, 33, pp.601~607 (2001)
- Hsueh WA, "Control of vascular cell proliferation and migration by PPAR-gamma : a new approach to the macrovascular complications of diabetes", Diabetes Care, 24, pp.392~397 (2001)
- Natarajan R, "Signaling mechanisms of nuclear factor-kappab-mediated activation of inflammatory genes by 13-hydroperoxyoctadecadienoic acid in cultured vascular smooth muscle cells", Arterioscler Thromb Vasc Biol, 21, pp.1408~1413 (2001)
- Chen YQ, "Sp1 sites mediate activation of the plasminogen activator inhibitor-1 promoter by glucose in vascular smooth muscle cells", J Biol Chem, 273, pp.8225~8231 (1998)
- Barnes JW, "O-GlcNAc transferase regulates angiogenesis in idiopathic pulmonary arterial hypertension", Int J Mol Sci, 20, pp.6299~ (2019)
- Du XL, "Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation", Proc Natl Acad Sci U S A, 97, pp.12222~12226 (2000)
- Suwanabol PA, "Transforming growth factor-β increases vascular smooth muscle cell proliferation through the Smad3 and extracellular signal-regulated kinase mitogen-activated protein kinases pathways", J Vasc Surg, 56, pp.446~454 (2012)
- Chen Y, "Augmentation of proliferation of vascular smooth muscle cells by plasminogen activator inhibitor type 1", Arterioscler Thromb Vasc Biol, 26, pp.1777~1783 (2006)
- James LR, "Flux through the hexosamine pathway is a determinant of nuclear factor kappaB-dependent promoter activation", Diabetes, 51, pp.1146~1156 (2002)
- Dela Justina V, "Increased O-linked N-acetylglucosamine modification of NF-κB and augmented cytokine production in the placentas from hyperglycemic rats", Inflammation, 40, pp.1773~1781 (2017)
- Yang WH, "NFkappaB activation is associated with its O-GlcNAcylation state under hyperglycemic conditions", Proc Natl Acad Sci U S A, 105, pp.17345~17350 (2008)
- Ramana KV, "Activation of nuclear factor-kappaB by hyperglycemia in vascular smooth muscle cells is regulated by aldose reductase", Diabetes, 53, pp.2910~2920 (2004)
- Jonason JH, "Post-translational regulation of Runx2 in bone and cartilage", J Dent Res, 88, pp.693~703 (2009)
- Nagel AK, "O-GlcNAc modification of the runt-related transcription factor 2(Runx2)links osteogenesis and nutrient metabolism in bone marrow mesenchymal stem cells", Mol Cell Proteomics, 13, pp.3381~3395 (2014)
