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


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< or =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.
Gaubius Laboratory TNO Biomedical Research, Leiden, The Netherlands.
Vincent
V
van Weel
Margreet
M
de Vries
Peter J
PJ
Voshol
Robert E
RE
Verloop
Paul H C
PH
Eilers
Victor W M
VW
van Hinsbergh
J Hajo
JH
van Bockel
Paul H A
PH
Quax
D000208:Acute Disease; D000818:Animals; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000235:genetics; D001158:Arteries / Q000254:growth & development; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003097:Collateral Circulation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology; D006614:Hindlimb / Q000098:blood supply; D006937:Hypercholesterolemia / Q000097:blood / Q000503:physiopathology*; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology*; D006949:Hyperlipidemias / Q000235:genetics / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007511:Ischemia / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018919:Neovascularization, Physiologic
D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; C052720:apolipoprotein E3 (Leidein); D002784:Cholesterol