Background: Vascular complications associated with diabetes are the major cause for the increased morbidity and mortality in diabetic patients. However, the progression of vascular complications in diabetes is not well understood. We aimed to investigate the biomechanical and biochemical changes associated with vascular dysfunction in diabetic rats. Methods: Male Wistar rats were randomly divided into two groups: normal control (n = 8) and fat-fed, streptozotocin-treated diabetic rats (n = 11). After 16 weeks, Peterson’s modulus of elasticity (Ep) and cross-sectional distensibility (CD) were calculated and compared between the two groups. Aortas were harvested from rats for histopathological and electron-microscopic analysis. Results: Collagenous fibers were scattered in the extracellular matrix and invaded the elastic lamina in the aortas of diabetic rats, suggesting a significant accumulation of collagen in diabetic vessels. Compared with normal rats, diabetic rats showed significantly reduced aortic distensibility (CD: 0.10 ± 0.04 vs. 0.17 ± 0.08 kPa–1, p = 0.033) and an increased aortic stiffness index (Ep: 0.25 ± 0.13 vs. 0.15 ± 0.05 × 106 dyn/cm2, p = 0.045). Ep was positively and CD negatively correlated with glucose and collagen in diabetic rats. Conclusions: In diabetic rats, elastic properties of the aorta are impaired, being closely related to hyperglycemia-induced vascular wall remodeling.

1.
Carson JL, Scholz PM, Chen AY, et al: Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery. J Am Coll Cardiol 2002;40:418–423.
2.
Vranes D, Cooper ME, Dilley RJ: Cellular mechanisms of diabetic vascular hypertrophy. Microvasc Res 1999;57:8–18.
3.
Meng J, Sakata N, Takebayashi S, et al: Advanced glycation end products of the Maillard reaction in aortic pepsin-insoluble and pepsin-soluble collagen from diabetic rats. Diabetes 1996;45:1037–1043.
4.
Laurent S, Boutouyrie P, Asmar R, et al: Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001;37:1236–1241.
5.
Shoji T, Emoto M, Shinohara K, Kakiya R, Tsujimoto Y: Diabetes mellitus, aortic stiffness, and cardiovascular mortality in end-stage renal disease. J Am Soc Nephrol 2001;12:2117–2124.
6.
Meaume S, Benetos A, Henry OF, Rudnichi A, Safar ME: Aortic pulse wave velocity predicts cardiovascular mortality in subjects >70 years of age. Arterioscler Thromb Vasc Biol 2001;21:2046–2050.
7.
Cruickshank K, Riste L, Anderson SG, et al: Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation 2002;106:2085–2090.
8.
van der Heijden-Spek JJ, Staessen JA, Fagard RH, et al: Effect of age on brachial artery wall properties differs from the aorta and is gender dependent: a population study. Hypertension 2000;35:637–642.
9.
Dernellis J, Panaretou M: Effects of thyroid replacement therapy on arterial blood pressure in patients with hypertension and hypothyroidism. Am Heart J 2002;143:718–724.
10.
Pannier BM, Avolio AP, Hoeks A, Mancia G, Takazawa K: Methods and devices for measuring arterial compliance in humans. Am J Hypertens 2002;15:743–753.
11.
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837–853.
12.
Singleton JR, Smith AG, Russell JW, Feldman EL: Microvascular complications of impaired glucose tolerance. Diabetes 2003;52:2867–2873.
13.
Zhang F, Ye C, Li G, et al: The rat model of type 2 diabetic mellitus and its glycometabolism characters. Exp Anim 2003;52:401–407.
14.
Larsen MO, Rolin B, Wilken M, Carr RD, Svendsen O: High-fat high-energy feeding impairs fasting glucose and increases fasting insulin levels in the Gottingen minipig: results from a pilot study. Ann NY Acad Sci 2002;967:414–423.
15.
Mythili MD, Vyas R, Akila G, Gunasekaran S: Effect of streptozotocin on the ultrastructure of rat pancreatic islets. Microsc Res Tech 2004;63:274–281.
16.
Sahin K, Onderci M, Tuzcu M, et al: Effect of chromium on carbohydrate and lipid metabolism in a rat model of type 2 diabetes mellitus: the fat-fed, streptozotocin-treated rat. Metabolism 2007;56:1233–1240.
17.
Bouvet C, Peeters W, Moreau S, deBloisc D, Moreau P: A new rat model of diabetic macrovascular complication. Cardiovasc Res 2007;73:504–511.
18.
Reed MJ, Meszaros K, Entes LJ, et al: A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism 2000;49:1390–1394.
19.
Noma T, Mizushige K, Yao L, et al: Alteration in aortic wall stiffness and accumulation of collagen during the prediabetic stage of type II diabetes mellitus in rats. Jpn Circ J 1999;63:988–993.
20.
Wolffenbuttel BH, Boulanger CM, Crijns FR, et al: Breakers of advanced glycation end products restore large artery properties in experimental diabetes. Proc Natl Acad Sci USA 1998;95:4630–4634.
21.
Karamitsos TD, Karvounis HI, Didangellos TP, et al: Usefulness of colour tissue Doppler imaging in assessing aortic elastic properties in type 1 diabetic patients. Diabet Med 2006;23:1201–1206.
22.
Karamitsos TD, Karvounis HI, Didangelos TP, et al: Aortic elastic properties are related to left ventricular diastolic function in patients with type 1 diabetes mellitus. Cardiology 2008;109:99–104.
23.
Tentolouris N, Liatis S, Moyssakis I, et al: Aortic distensibility is reduced in subjects with type 2 diabetes and cardiac autonomic neuropathy. Eur J Clin Invest 2003;33:1075–1083.
24.
Toutouzas K, Stefanadis C, Tsiamis E, et al: Aortic pressure-diameter relation in patients with non-insulin dependent diabetes mellitus: new insights. Diabetologia 2000;43:1070–1075.
25.
Candido R, Allen TJ, Lassila M, et al: Irbesartan but not amlodipine suppresses diabetes-associated atherosclerosis. Circulation 2004;109:1536–1542.
26.
Kochakian M, Manjula BN, Egan JJ: Chronic dosing with aminoguanidine and novel advanced glycosylation end product-formation inhibitors ameliorates cross-linking of tail tendon collagen in STZ-induced diabetic rats. Diabetes 1996;45:1694–1700.
27.
Reddy GK: AGE-related cross-linking of collagen is associated with aortic wall matrix stiffness in the pathogenesis of drug-induced diabetes in rats. Microvasc Res 2004;68:132–142.
28.
Marsh JN, Takiuchi S, Lin SJ, Lanza GM, Wickline SA: Ultrasonic delineation of aortic microstructure: the relative contribution of elastin and collagen to aortic elasticity. J Acoust Soc Am 2004;115:2032–2040.
29.
Umezono T, Toyoda M, Kato M, et al: Glomerular expression of CTGF, TGF-beta 1 and type IV collagen in diabetic nephropathy. J Nephrol 2006;19:751–757.
30.
Langham RG, Kelly DJ, Gow RM, et al: Transforming growth factor-beta in human diabetic nephropathy: effects of ACE inhibition. Diabetes Care 2006;29:2670–2675.
31.
Zhao Q, Chen N, Wang WM, Lu J, Dai BB: Effect of transforming growth factor-beta on activity of connective tissue growth factor gene promoter in mouse NIH/3T3 fibroblasts. Acta Pharmacol Sin 2004;25:485–489.
32.
Xie S, Sukkar MB, Issa R, et al: Regulation of TGF-beta 1-induced connective tissue growth factor expression in airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2005;288:L68–L76.
33.
Eddy AA: Molecular basis of renal fibrosis. Pediatr Nephrol 2000;15:290–301.
34.
Alla F, Kearney-Schwartz A, Radauceanu A, et al: Early changes in serum markers of cardiac extra-cellular matrix turnover in patients with uncomplicated hypertension and type II diabetes. Eur J Heart Fail 2006;8:147–153.
35.
Samuel CS: Relaxin: antifibrotic properties and effects in models of disease. Clin Med Res 2005;3:241–249.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.