Diabetes alters the expression of partial vasoactivators in cerebral vascular disease susceptible regions of the diabetic rat

Diabetology & Metabolic Syndrome

Yuchen Wu¹  Hui Wan¹  Qiujiang Xi¹  Huoyou Hu¹  Rongwei Yang¹  Renshi Xu¹ 

[1] Department of Neurology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China

关键词: Cerebral vascular disease;    Endothelial activators;    Endothelial dysfunction;    Diabetes;   

Others  :  812626
DOI  :  10.1186/1758-5996-5-63

 received in 2013-04-14, accepted in 2013-10-17,  发布年份 2013

【 摘 要 】

Background

The pathogenesis between cerebral vascular disease (CVD) and the endothelial dysfunction (ETD) remains elusive in diabetes. Therefore, we investigated the expression of partial vasoactivators which be closely relative to ETD in CVD susceptible brain regions in the diabetic rat. The aim was to search some possible pathogenesis.

Methods

Diabetes was induced by a single intraperitoneal injection of streptozotocin and a high lipid/sugar diet. The expression of vasoactivators ET-1, CGRP, VCAM-1, ICAM-1 and P-selectin were assessed by immunohistochemical staining and measurement of optic density of positive cells in the frontal and temporal lobe, basal ganglia and thalamus at 4 weeks after establishment of the diabetic model.

Results

The expression of ET-1, VCAM-1, ICAM-1 and P-selectin significantly increased and CGRP significantly decreased in the diabetic group, and the expression of these vasoactivators was significantly different among the frontal, temporal lobe, basal ganglia and thalamus, and among the emotion, splanchno-motor and neuroendocrine center in the diabetic group.

Conclusions

Diabetes alters the expression of partial vasoactivators in cerebral vascular disease susceptible regions of the diabetic rat. Therefore, we suggested that CVD complications in diabetes are partly caused by ETD via an imbalance expression of endothelial vasoactivators, which might be associated with dysfunction of emotion, autonomic nerve and endocrine center. However, further studies are warranted.

【 授权许可】

   
2013 Xu et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Wild S, Roglic G, Green A, Sicree R, King H: Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004, 27(5):1047-1053.
• [2]Wong WT, Wong SL, Tian XY, Huang Y: Endothelial dysfunction: the common consequence in diabetes and hypertension. J Cardiovasc Pharmacol 2010, 55(4):300-3007.
• [3]van den Oever IA, Raterman HG, Nurmohamed MT, Simsek S: Endothelial dysfunction, inflammation, and apoptosis in diabetes mellitus. Mediators Inflamm 2010, 2010:792393.
• [4]Cohen RA, Tong X: Vascular oxidative stress: the common link in hypertensive and diabetic vascular disease. J Cardiovasc Pharmacol 2010, 55(4):308-316.
• [5]Tan KC, Chow WS, Ai VH, Lam KS: Effects of angiotensin II receptor antagonist on endothelial vasomotor function and urinary albumin excretion in type 2 diabetic patients with microalbuminuria. Diabetes Metab Res Rev 2002, 18(1):71-76.
• [6]Verma S, Anderson TJ: Fundamentals of endothelial function for the clinical cardiologist. Circulation 2002, 105(5):546-549.
• [7]Zhang M, Lv XY, Li J, Xu ZG, Chen L: The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Exp Diabetes Res 2008, 2008:704045.
• [8]Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Gadbois TM, Reaven GM: A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism 2000, 49(11):1390-1394.
• [9]Wedgwood S, McMullan DM, Bekker JM, Fineman JR, Black SM: Role for endothelin-1-induced superoxide and peroxynitrite production in rebound pulmonary hypertension associated with inhaled nitric oxide therapy. Circ Res 2001, 89(4):357-364.
• [10]Romero M, Jiménez R, Sánchez M, López-Sepúlveda R, Zarzuelo MJ, O’Valle F, Zarzuelo A, Pérez-Vizcaíno F, Duarte J: Quercetin inhibits vascular superoxide production induced by endothelin-1: Role of NADPH oxidase, uncoupled eNOS and PKC. Atherosclerosis 2009, 202(1):58-67.
• [11]Brain SD, Williams TJ, Tippins JR, Morris HR, MacIntyre I: Calcitonin gene-related peptide is a potent vasodilator. Nature 1985, 313(5997):54-56.
• [12]McCulloch J, Uddman R, Kingman TA, Edvinsson L: Calcitonin gene-related peptide: functional role in cerebrovascular regulation. Proc Natl Acad Sci USA 1986, 83(15):5731-5735.
• [13]Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, Iiyama M, Davis V, Gutierrez-Ramos JC, Connelly PW, Milstone DS: A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest 2001, 107(10):1255-1262.
• [14]Iademarco MF, McQuillan JJ, Rosen GD, Dean DC: Characterization of the promoter for vascular cell adhesion molecule-1 (VCAM-1). J Biol Chem 1992, 267(23):16323-16329.
• [15]van Buul JD, Voermans C, van den Berg V, Anthony EC, Mul FP, van Wetering S, van der Schoot CE, Hordijk PL: Migration of human hematopoietic progenitor cells across bone marrow endothelium is regulated by vascular endothelial cadherin. J Immunol 2002, 168(2):588-596.
• [16]van Wetering S, van den Berk N, van Buul JD, Mul FP, Lommerse I, Mous R, ten Klooster JP, Zwaginga JJ, Hordijk PL: VCAM-1-mediated Rac signaling controls endothelial cell-cell contacts and leukocyte transmigration. Am J Physiol Cell Physiol 2003, 285(2):C343-C352.
• [17]Madonna R, Pandolfi A, Massaro M, Consoli A, De Caterina R: Insulin enhances vascular cell adhesion molecule-1 expression in human cultured endothelial cells through a pro-atherogenic pathway mediated by p38 mitogen-activated protein-kinase. Diabetologia 2004, 47(3):532-536.
• [18]Okouchi M, Okayama N, Shimizu M, Omi H, Fukutomi T, Itoh M: High insulin exacerbates neutrophil-endothelial cell adhesion through endothelial surface expression of intercellular adhesion molecule-1 via activation of protein kinase C and mitogen-activated protein kinase. Diabetologia 2002, 45(4):556-559.
• [19]Rahman A, Fazal F: Hug tightly and say goodbye: role of endothelial ICAM-1 in leukocyte transmigration. Antioxid Redox Signal 2009, 11(4):823-839.
• [20]Doran AC, Meller N, McNamara CA: Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arterioscler Thromb Vasc Biol 2008, 28(5):812-819.
• [21]Galkina E, Ley K: Vascular adhesion molecules in atherosclerosis. Arterioscler Thromb Vasc Biol 2007, 27:2292-2301.
• [22]Pi X, Lockyer P, Dyer LA, Schisler JC, Russell B, Carey S, Sweet DT, Chen Z, Tzima E, Willis MS, Homeister JW, Moser M, Patterson C: Bmper inhibits endothelial expression of inflammatory adhesion molecules and protects against atherosclerosis. Arterioscler Thromb Vasc Biol 2012, 32(9):2214-2222.
• [23]Lawson C, Wolf S: ICAM-1 signaling in endothelial cells. Pharmacol Rep 2009, 61(1):22-32.
• [24]Deem TL, Cook-Mills JM: Vascular cell adhesion molecule 1 (VCAM-1) activation of endothelial cell matrix metalloproteinases: role of reactive oxygen species. Blood 2004, 104(8):2385-2393.
• [25]Setiadi H, McEver RP: Signal-dependent distribution of cell surface P-selectin in clathrin-coated pits affects leukocyte rolling under flow. J Cell Biol 2003, 163(6):1385-1395.
• [26]Yang SX, Yan J, Deshpande SS, Irani K, Lowenstein CJ: Rac1 regulates the release of Weibel-Palade Bodies in human aortic endothelial cells. Chin Med J (Engl) 2004, 117(8):1143-1150.
• [27]Panés J, Kurose I, Rodriguez-Vaca D, Anderson DC, Miyasaka M, Tso P, Granger DN: Diabetes exacerbates inflammatory responses to ischemia-reperfusion. Circulation 1996, 93(1):161-167.
• [28]Kaplanski G, Farnarier C, Benoliel AM, Foa C, Kaplanski S, Bongrand P: A novel role for E- and P-selectins: shape control of endothelial cell monolayers. J Cell Sci 1994, 107(Pt 9):2449-2457.
• [29]Pasceri V, Willerson JT, Yeh ET: Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000, 102(18):2165-2168.
• [30]Rodriguez CJ, Miyake Y, Grahame-Clarke C, Di Tullio MR, Sciacca RR, Boden-Albala B, Sacco RL, Homma S: Relation of plasma glucose and endothelial function in a population-based multiethnic sample of subjects without diabetes mellitus. Am J Cardiol 2005, 96(9):1273-1277.
• [31]Tooke JE, Hannemann MM: Adverse endothelial function and the insulin resistance syndrome. J Intern Med 2000, 247(4):425-431.
• [32]Blankenberg S, Barbaux S, Tiret L: Adhesion molecules and atherosclerosis. Atherosclerosis 2003, 170(2):191-203.
• [33]Simionescu M: Implications of early structural-functional changes in the endothelium for vascular disease. Arterioscler Thromb Vasc Biol 2007, 27(2):266-274.
• [34]Raghavan VA: Insulin resistance and atherosclerosis. Heart Fail Clin 2012, 8(4):575-587.
• [35]Rask-Madsen C, King GL: Mechanisms of disease: endothelial dysfunction in insulin resistance and diabetes. Nat Clin Pract Endocrinol Metab 2007, 3(1):46-56.
• [36]Libby P, Ridker PM, Maseri A: Inflammation and atherosclerosis. Circulation 2002, 105(9):1135-1143.
• [37]Perez del Villar C, Garcia Alonso CJ, Feldstein CA, Juncos LA, Romero JC: Role of endothelin in the pathogenesis of hypertension. Mayo Clin Proc 2005, 80(1):84-96.
• [38]Wedgwood S, Dettman RW, Black SM: ET-1 stimulates pulmonary arterial smooth muscle cell proliferation via induction of reactive oxygen species. Am J Physiol Lung Cell Mol Physiol 2001, 281(5):L1058-L1067.