Platelet and megakaryocyte changes in cholesterol-induced experimental atherosclerosis.

Abstract

Rabbits were fed either 2 g cholesterol in 10 ml olive oil daily with normal diet (n = 5) or normal diet alone (n = 5). After 12 weeks, the cholesterol-fed animals had developed fatty plaques involving 24% ± 4% of the surface area of the aorta; the control animals had none. Mean platelet volume was significantly smaller (p < 0.04) in the cholesterol-fed animals (4.1 ± 0.3 fl) compared with the controls (4.8 ± 0.4 fl). The heterogeneity of the average volume distributions of the two groups, characterized by the statistical parameters of the coefficient of variation, skewness, and kurtosis, was also significantly different. Platelet count was significantly higher (p < 0.001) in the cholesterol-fed group (7.48 ± 1.06 x 10" platelets/liter blood) compared to the control group (4.86 ± 0.60 x 10 11 platelets/liter blood). Mean megakaryocyte cytoplasmic volume was significantly larger (p < 0.001) in the cholesterol-fed rabbits (12,262 ± 1485 fl) compared with controls (6,814 ± 761 fl). The range of cytoplasmic volumes was also significantly increased in the cholesterol-fed rabbits. A significant (p < 0.01) increase in mean megakaryocyte nuclear volume in the cholesterol-fed animals was accompanied by a nonsignificant increase in mean nuclear DNA content: 30.2 ± 3.7 N compared with a control value of 23.6 ± 4.0 N. This evidence indicates that a high cholesterol diet in rabbits is associated with changes in platelet production from megakaryocytes as well with as the development of atherosclerosis. (Arteriosclerosis 5:604-612, November/December 1985) P latelets in vascular disease have increased reactivity in both human and animal models. 12 The cause of this increased reactivity may either be an effect of vessel wall changes on normal platelets or be related to an intrinsic change in the platelets themselves. In humans, the increased platelet reactivity has been associated with platelet size changes 1 which have been confirmed in recent studies.3 " 5 This evidence suggests that there may be alterations in platelet production in vascular disease. Two further observations support this hypothesis. Men who suffered sudden cardiac death associated with atheromatous arteries had larger megakaryocytes than a control group who died unexpectedly from unnatural causes.6 Similar large megakaryocytes, which produced larger than normal platelets, were also observed in men with acute myocardial infarction.

The regulation of megakaryocyte polyploidization and its implications for coronary artery occlusion

“…It has also been demonstrated in rabbits and guinea pigs that similar changes in MK size and ploidy can be induced by feeding animals a high cholesterol diet for prolonged periods of time [56,57]. Furthermore, acute destruction of platelets with an anti-platelet serum in rabbits fed a high cholesterol diet led to a further increase in the size and DNA content of MKs and to an acceleration of atherogenesis (Fig.…”

The Relationship between the Plasma PCSK9 Levels and Platelet Indices in Patients with Stable Coronary Artery Disease

“…Animal models with a high cholesterol diet show a significant increase in the PLT count compared to those fed the normal diet 19) . The positive correlation between the PLT count and LDL-C level and multiple metabolic factors reported in population studies suggests a potential link between the PLT count and dyslipidemia 1,2) .…”

Increased Platelet Cholesterol and Decreased Percentage Volume of Platelets as a Secondary Risk Factor for Coronary Artery Disease

“…Atherogenic lipoproteins -low-density lipid (LDL) and very low-density lipid cholesterol -enhance platelet activation in vitro [3][4][5] and increase platelet cholesterol. Previous studies using animal models have shown that increased platelet cholesterol is due to the uptake of circulating cholesterol by megakaryocytes which then incorporate into future platelets [6,7] .…”