Simvastatin Preserves Coronary Endothelial Function in Hypercholesterolemia in the Absence of Lipid Lowering

Abstract

Abstract-Recent evidence suggests that some benefit from the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may occur independent of lipid lowering. We aimed to determine the effect of simvastatin on coronary endothelial function, endothelial NO synthase (eNOS) expression, and oxidative stress in experimental hypercholesterolemia (HC) in the absence of cholesterol lowering. Pigs were randomized to 3 experimental groups: normal diet (N group), high cholesterol diet (HC group), and HC diet with simvastatin (HCϩS group) for 12 weeks. Low density lipoprotein cholesterol was similarly increased in the HC and HCϩS groups compared with the N group. In vitro analysis of coronary large-and small-vessel endothelium-dependent vasorelaxation was performed.

Evidence for an Independent and Cumulative Effect of Postprandial Hypertriglyceridemia and Hyperglycemia on Endothelial Dysfunction and Oxidative Stress Generation

“…In addition, the diabetic patients were retested after 3 to 6 days or 3 months of simvastatin treatment. The objective of the short-term simvastatin treatment was to evaluate a possible direct effect of the drug on endothelial function, possibly through an inhibition of oxidative stress, 15,16 whereas the long-term treatment was aimed to also evaluate the effect of decreased postprandial hypertriglyceridemia. 17 …”

Increased tissue kallikrein levels in type 2 diabetes

“…In addition, we obtained samples of right atrial appendage from some patients to perform immunohistochemistry for tissue kallikrein and to measure tissue kallikrein mRNA levels. Because a large proportion of these patients were receiving 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor (statin) therapy, and because statin therapy affects endothelial function and possibly also kinin generation at the endothelial surface [11,12], the association between current statin use and KKS variables was also evaluated.…”

HDL-Mediated Protection of Coronary Vasodilator Response to Adenosine in the Hypercholesterolemic Swine

“…However, reports, where a lower cholesterol supplement for a longer diet period is also able to ensure an almost tenfold LDL elevation [41], suggest that the relation between cholesterol addition to diet, or duration of diet and the increase of total cholesterol and its lipoprotein-fractions in plasma is not direct. In fact, a so high LDL plasma level in this study was reached independently of diet duration, being comparable in HF and IHF groups and it can be likely attributed to liver lipid metabolism adaptations to an excessive cholesterol intake.…”

“…In fact, a so high LDL plasma level in this study was reached independently of diet duration, being comparable in HF and IHF groups and it can be likely attributed to liver lipid metabolism adaptations to an excessive cholesterol intake. The same considerations can be done for HDL elevation: a great variability is present in different studies of swine hypercholesterolemia [40] [41]. To clarify these results a primary role of increased hepatic synthesis of HDL in alternate diet regimen and a better adaptation of liver metabolism to plasma lipid overload as compared to continuous cholesterol administration can be reasonably sustained [42].…”