The influence of chylomicron remnants on endothelial cell function in the isolated perfused rat aorta

Abstract

. (1998). The influence of chylomicron remnants on endothelial cell function in the isolated perfused rat aorta. Atherosclerosis, 139 (2)(2) AbstractA system for the perfusion of the isolated rat aorta which allowed the study of both the uptake of chylomicron remnants by the artery wall and their effects on endothelial function was developed. Perfusion for 2 h with 125 I-labelled native or oxidised (by treatment with copper sulphate) chylomicron remnants showed that small amounts became associated with the artery wall (0.1119 0.034 and 0.216 9 0.082 ng protein/mg tissue, respectively). Tests on endothelial function were carried out in vessel rings prepared after perfusion of the aortas in the presence or absence of chylomicron remnants for 2 h. After perfusion of the vessels with oxidised chylomicron remnants, the maximum response to phenylephrine (PE) was significantly increased (from 0.34 9 0.06 to 0.5190.04 g/mg tissue; PB0.05), while the maximum % relaxation to carbachol (CCh) was significantly decreased (from 91.6 9 2.4 to 71.5 9 7.2; PB 0.05) and the response to S-nitroso-N-acetylpenicillimine (SNAP) was unaffected. Perfusion with native chylomicron remnants showed a tendency to induce similar effects, although the changes observed did not reach statistical significance. As the lipoproteins were not present in the solution bathing the vessel rings during these tests, these effects can be attributed to perfusion of the aortas with chylomicron remnants, despite only small quantities being associated with the artery wall. The results suggest that oxidised chylomicron remnants influence vascular endothelial function by interfering with the L-arginine-nitric oxide (NO) pathway. The observed potentiation of contraction to PE may be due to inhibition of the basal release of NO or to the release of contractile factors. These findings support a role for dietary lipoproteins in the modulation of endothelial cell function which occurs in the pathogenesis of atherosclerosis.

Xuezhikang, an Extract of Cholestin, Protects Endothelial Function Through Antiinflammatory and Lipid-Lowering Mechanisms in Patients With Coronary Heart Disease

“…Acutely impaired endothelium-dependent vasodilation after a high-fat meal has been found to be associated with postprandial hypertriglyceridemia. 2,13,14 Furthermore, postprandial hypertriglyceridemia may induce endothelial dysfunction through the direct effects of triglyceride-rich lipoproteins 3,4 and increasing oxidative stress in circulation. 1,15,16 These data indicate that lowering postprandial triglyceride concentration may lead to improvement of endothelial function.…”

“…1,2 Moreover, postprandial triglyceride-rich lipoproteins and remnants directly impair endothelium-dependent vasodilation in animal models. 3,4 In addition, treatment strategies for lowering postprandial hypertriglyceridemia may lead to a reduction in CHD risk. 5 Inflammation is closely associated with endothelial dysfunction and atherosclerosis.…”

Effects of chylomicrons and chylomicron remnants on endothelium-dependent relaxation of rat aorta

“…As mentioned earlier, in a previous study we found chylomicron remnants to potentiate contraction to phenylephrine in an Ž . endothelium-dependent manner Grieve et al, 1997a . This effect was further potentiated when nitric oxide release was completely blocked by N v -nitro-L-arginine which rules out any possible effect on basal nitric oxide production.…”

Double-Blind Randomized Clinical Trial of the Effects of Ezetimibe on Postprandial Hyperlipidaemia and Hyperglycaemia

“…The secondary endpoints were glucose metabolism markers, inflammatory markers, and the serum adiponectin level. For the lipid metabolism Postprandial hyperglycaemia and hypertriglyceridaemia are also recognized as the risk for cardiovascular events related to postprandial endothelial dysfunction, in addition to classical risk factors [6][7][8][9][10] . Lipoprotein particles undergo partial hydrolysis predominantly through the action of lipoprotein lipase (LPL), forming smaller and denser particles known as remnants that are believed to be more atherogenic than larger triglyceride-rich lipoproteins (TRL).…”