on March 30, 2006
Published online before print March 30, 2006, doi: 10.1161/01.ATV.0000219234.78165.85
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 30, 2004
Accepted on March 9, 2006
Hypercholesterolemia Reduces Collateral Artery Growth More Dominantly Than Hyperglycemia or Insulin Resistance in Mice
Vincent van Weel ;
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.
* To whom correspondence should be addressed. 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 (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.
Key words: arteriogenesis • cholesterol • collateral circulation • diabetes • NOD mice • peripheral vascular disease
This article has been cited by other articles:
 |
|
 |
|
  O. A. Stone, C. Richer, C. Emanueli, V. van Weel, P. H.A. Quax, R. Katare, N. Kraenkel, P. Campagnolo, L. S. Barcelos, M. Siragusa, et al. Critical Role of Tissue Kallikrein in Vessel Formation and Maturation: Implications for Therapeutic Revascularization Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 657 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S H Schirmer, F C van Nooijen, J J Piek, and N van Royen Stimulation of collateral artery growth: travelling further down the road to clinical application Heart, February 1, 2009; 95(3): 191 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. van Oostrom, O. van Oostrom, P. H. A. Quax, M. C. Verhaar, and I. E. Hoefer Insights into mechanisms behind arteriogenesis: what does the future hold? J. Leukoc. Biol., December 1, 2008; 84(6): 1379 - 1391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|