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Hypercholesterolemia reduces collateral artery growth more dominantly than hyperglycemia or insulin resistance in mice

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Author: Weel, V. van · Vries, M. de · Voshol, P.J. · Verloop, R.E. · Eilers, P.H.C. · Hinsbergh, V.W.M. van · Bockel, J.H. van · Quax, P.H.A.
Type:article
Date:2006
Institution: TNO Kwaliteit van Leven
Source:Arteriosclerosis, Thrombosis, and Vascular Biology, 6, 26, 1383-1390
Identifier: 239307
doi: doi:10.1161/01.ATV.0000219234.78165.85
Keywords: Biology · Biomedical Research · Arteriogenesis · Cholesterol · Collateral circulation · Diabetes · NOD mice · Peripheral vascular disease · Glucose · Streptozocin · Triacylglycerol · Lipid · Angiogenesis · Angiography · Animal model · Artery occlusion · Cholesterol blood level · Controlled study · Diabetes mellitus · Diet · Fatty acid blood level · Femoral artery · Glucose blood level · Glucose metabolism · Hypercholesterolemia · Hyperglycemia · Insulin blood level · Insulin resistance · Laser Doppler flowmetry · Lipid metabolism · Male · Mouse · Nonhuman · Postoperative period · Blood · Collateral circulation · Comparative study · Experimental diabetes mellitus · Genetics · Growth, development and aging · Metabolism · Mouse strain · Pathophysiology · Physiology · Vascularization · Acute Disease · Animals · Apolipoprotein E3 · Apolipoproteins E · Arteries · Blood Glucose · Cholesterol · Collateral Circulation · Diabetes Mellitus, Experimental · Hindlimb · Hypercholesterolemia · Hyperglycemia · Hyperlipidemias · Insulin · Insulin Resistance · Ischemia · Lipids · Male · Mice · Mice, Inbred Strains · Neovascularization, Physiologic

Abstract

OBJECTIVE - Collateral artery development (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease, may be deregulated by vascular risk factors, eg, diabetes or hypercholesterolemia. Here, we compared the effects of either disturbed glucose metabolism or disturbed lipid metabolism on arteriogenesis. METHODS AND RESULTS - Femoral artery occlusion was performed in streptozotocin(STZ)-treated mice, nonobese diabetic (NOD) mice, and insulin-resistant Ob/Ob mice on regular diet, and APOE3*Leiden mice on different hypercholesterolemic diets. Angiography and laser Doppler perfusion analysis of hindlimbs were performed postoperatively. Surprisingly, angiographic arteriogenesis was not impaired in diabetic and insulin-resistant mice. Perfusion recovery in STZ-treated and Ob/Ob mice was only decreased by 19% and 16%, respectively (P<0.05). Furthermore, perfusion recovery was unchanged between high-glycemic and mild-glycemic NOD mice. Angiographic arteriogenesis in APOE3*Leiden mice, however, was markedly impaired at 7 days and 14 days (P≤0.01). Correspondingly, perfusion recovery was 41% decreased in APOE3*Leiden mice (P<0.05). There was an inverse correlation of perfusion recovery with plasma cholesterol (P=0.02), but not with triglyceride, free fatty acid, glucose, or insulin levels. CONCLUSIONS - Hypercholesterolemia reduces arteriogenesis more dominantly than hyperglycemia or hyperinsulinemia in mice. This suggests that a disturbed lipid metabolism as observed in diabetic patients might be crucial for the impairment of collateral formation. © 2006 American Heart Association, Inc. Chemicals / CAS: cholesterol, 57-88-5; glucose, 50-99-7, 84778-64-3; insulin, 9004-10-8; streptozocin, 18883-66-4; lipid, 66455-18-3; Apolipoprotein E3; Apolipoproteins E; Blood Glucose; Cholesterol, 57-88-5; Insulin, 11061-68-0; Lipids; apolipoprotein E3 (Leidein)