Effect of gemfibrozil on peripheral atherosclerosis and platelet activation in a pig model of hyperlipidemia

Abstract

Gemfibrozil delayed the development of peripheral atherosclerotic plaque, normalised the impaired lipid profile induced by the hyperlipidemic diet and did not show a functionally detectable platelet pro-activating effect able to increase platelet-fibrinogen binding.

Complex porcine model of atherosclerosis: Induction of early coronary lesions after long-term hyperlipidemia without sustained hyperglycemia

“…Interestingly, another study (20) with an observation period of up to 50 weeks (also using minipigs) demonstrated cholesterol-induced accelerated atherosclerosis at certain vascular sites (eg, abdominal aorta and mesenteric arteries) but no significant atherosclerosis in the coronary arteries. Studies in domestic pigs, with observation periods comparable with our study (up to 13 weeks) and LDL cholesterol levels between 4.6 mmol/L and 9.3 mmol/L (3.3 mmol/L in our study), induced vascular lesions resembling early states of atherosclerotic disease without significant luminal narrowing (8,22,23). Racial and physiological differences between animal models (juvenile domestic pig versus mature minipig) and the varying durations of diet may explain the differences observed in coronary artery histopathology in these studies.…”

“…Hyperlipidemia was reported to induce atherosclerotic coronary lesions in minipigs as well as in domestic swine (8,(18)(19)(20). In these studies, hyperlipidemic diet compositions (1% to 6% cholesterol, high proportion of fat, high percentage of saturated fatty acids), duration of feeding and observation periods (six to 50 weeks) varied markedly.…”

“…To create such an atherosclerotic animal model, pigs in the present study were fed a special atherogenic chow to induce hypercholesterolemia, because a number of studies have shown that hypercholesterolemia is associated with the development of atherosclerosis (5)(6)(7)(8). Diabetes is another major risk factor for the development of atherosclerosis and, because streptozotocin (STZ) was successfully used to induce diabetes in other studies (6,9-13), we used a previously described STZ injection protocol (6).…”

Rupture of the Atherosclerotic Plaque

“…In time, pigs develop atherosclerosis even on a normal porcine diet. [51][52][53][54][55] When fed cholesterol, they develop plasma cholesterol levels and atherosclerotic lesions that are similar to those seen in humans. The white Belgian pig variety also exhibits sudden coronary death when under stress.…”

Animal Models as Tools for Translational Research: Focus on Atherosclerosis, Metabolic Syndrome and Type-II Diabetes Mellitus

“…In this regard, pig, is a considered a very good model of human atherosclerosis, because it is similar to humans in terms of body size and other physiological features (see review [122]). Pigs spontaneously develop atherosclerosis even on a normal porcine diet and dietary modification lead to sever atherosclerosis [123]. As humans, pigs transport most cholesterol in LDL-C and dietary modification alters their plasma lipoproteins closely resemble those occurring in humans.…”