Haemodynamically significant plaque formation and regional endothelial dysfunction in cholesterol-fed ApoE-/- mice.
Flow-mediated vasodilation is suggested as one of the mechanisms involved in arterial expansive remodelling, which is thought to be a defence mechanism in atherogenesis. In the present study, we tested the hypothesis that lumen obstructive plaque formation is associated with failure of NO (nitric oxide)-dependent vasodilation in conduit vessels. Cardiac function and aortic root flow velocities were assessed using high-resolution echocardiography and two-dimensional-guided pulsed Doppler in ApoE(-/-) (apolipoprotein E-deficient) mice fed a standard or high-cholesterol diet. Endothelial function in the proximal and mid-descending aortic regions was studied using a myograph technique. Flow velocity at the aortic root of cholesterol-fed ApoE(-/-) mice was significantly increased as a result of lumen narrowing, detected via histological analysis. NO-dependent vasodilatory responses were selectively impaired in the atherosclerosis-prone vascular regions in cholesterol-fed ApoE(-/-) mice. In conclusion, consumption of a high-cholesterol diet results in lumen obstructive plaque formation in ApoE(-/-) mice, which significantly alters aortic root haemodynamics. This phenomenon is associated with impaired NO-dependent vasodilation in vessel segments known to be prone to atherosclerosis.
Johansson
Maria E
ME
Department of Physiology, Institute of Physiology and Pharmacology, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
Hägg
Ulrika
U
Wikström
Johannes
J
Wickman
Anna
A
Bergström
Göran
G
Gan
Li-ming
LM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D001057:Apolipoproteins E / Q000235:genetics*; D001158:Arteries; D001161:Arteriosclerosis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D001794:Blood Pressure; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003331:Coronary Vessels / Q000378:metabolism; D018619:Echocardiography, Doppler, Pulsed; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009599:Nitroprusside / Q000494:pharmacology; D011897:Random Allocation; D014665:Vasodilator Agents / Q000494:pharmacology
D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine