Haemodynamically significant plaque formation and regional endothelial dysfunction in cholesterol-fed ApoE−/− mice

Abstract

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.

Proximal to Middle Left Coronary Artery Flow Velocity Ratio, As Assessed Using Color Doppler Echocardiography, Predicts Coronary Artery Atherosclerosis in Mice

“…11 Interestingly, this observation also holds true in the aortic roots in atherosclerotic mouse models. 14 Recently, velocity ratio between prestenotic and stenotic flow using CDE was applied to determine the degree of restenosis in patients undergoing angioplasty. 4,5 Our present findings reveal that flow velocity in the proximal LCA increases with age in atherosclerotic mice, although it remains unaffected in the middle part of LCA, a phenomenon not evident in the nonatherosclerotic C57 control animals.…”

Functional and Morphologic Imaging of Coronary Atherosclerosis in Living Mice Using High-Resolution Color Doppler Echocardiography and Ultrasound Biomicroscopy

“…Echocardiography was performed using a high-frequency 15-MHz linear transducer (Entos CL15-7, Philips Medical Systems, Bothell, Washington) connected to an ultrasound system (ATL-HDI5000, Philips Medical Systems). Standard basic echocardiography measurements and calculations were performed as described previously (12).…”

Vascular Kinin B1 and B2 Receptors Determine Endothelial Dysfunction through Neuronal Nitric Oxide Synthase

“…It is worth noting that non-selective NOS inhibition and B 1 - or B 2 -kinin receptors antagonists led to vascular contraction. These vascular responses further support that inhibition of the main vasodilation pathway favors contractile mechanisms, in which the oxidative stress is well-known to play a dysfunctional role in several vascular disorders (Johansson et al, 2005; Loria et al, 2014). Moreover, a reasonable explanation for selecting ACh as the agonist to trigger the vasorelaxation in the present study is the well-known NOS activation by muscarinic pathway whereas, the vascular response of agonists of kinin receptors is still controversial in aorta of different species, where it produces vasoconstriction (Levesque et al, 1993; Felipe et al, 2007) or vasodilation (Tsutsui et al, 2000).…”