This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 26/6/1383    most recent 01.ATV.0000219234.78165.85v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Weel, V. Articles by Quax, P. H.A. Search for Related Content PubMed PubMed Citation Articles by van Weel, V. Articles by Quax, P. H.A.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1383.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Hypercholesterolemia Reduces Collateral Artery Growth More Dominantly Than Hyperglycemia or Insulin Resistance in Mice

Vincent van Weel; Margreet de Vries; Peter J. Voshol; Robert E. Verloop; Paul H.C. Eilers; Victor W.M. van Hinsbergh; J. Hajo van Bockel; Paul H.A. Quax

From Gaubius Laboratory TNO Biomedical Research (V.v.W., M.d.V., R.E.V., V.W.M.v.H., P.H.A.Q.), Leiden, the Netherlands; Department of Surgery (V.v.W., J.H.v.B., P.H.A.Q.), Leiden University Medical Center (LUMC), Leiden, the Netherlands; Department of Endocrinology (P.J.V.), LUMC, Leiden, the Netherlands; Department of Physiology (V.W.M.v.H.), Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, the Netherlands; Department of Medical Statistics (P.H.C.E.), LUMC, Leiden, the Netherlands.

Correspondence to Dr P.H.A. Quax, Gaubius Laboratory, TNO Biomedical Research, P.O. Box 2215, 2301CE Leiden, the Netherlands. E-mail PHA.Quax{at}pg.tno.nl

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 (P0.01). 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.

Collateral formation (arteriogenesis) may be deregulated by vascular risk factors, eg, diabetes or hypercholesterolemia. Here, we found that hypercholesterolemia reduces arteriogenesis more dominantly than hyperglycemia or hyperinsulinemia in mice. This suggests that a disturbed lipid metabolism as observed in diabetics might be crucial for deregulation of arteriogenesis.

Key Words: arteriogenesis • cholesterol • collateral circulation • diabetes • NOD mice • peripheral vascular disease

This article has been cited by other articles:

				X. Zhou, H. G. Bohlen, S. J. Miller, and J. L. Unthank NAD(P)H oxidase-derived peroxide mediates elevated basal and impaired flow-induced NO production in SHR mesenteric arteries in vivo Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1008 - H1016. [Abstract] [Full Text] [PDF]

				S. M. Vartanian and R. Sarkar Therapeutic Angiogenesis Vascular and Endovascular Surgery, July 1, 2007; 41(3): 173 - 185. [Abstract] [PDF]

				S. J. Miller, L. E. Norton, M. P. Murphy, M. C. Dalsing, and J. L. Unthank The role of the renin-angiotensin system and oxidative stress in spontaneously hypertensive rat mesenteric collateral growth impairment Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2523 - H2531. [Abstract] [Full Text] [PDF]