Platelet Activity In Vivo in Hyperlipoproteinemia – Importance of Combined Hyperlipidemia

Abstract

SummaryPlatelet hyperactivity in vitro is found in patients with isolated hypercholesterolemia. It is, however, less well established if platelet activity in vivo is enhanced, and if there are differences between various types of hyperlipoproteinemia.Platelet function in vivo was studied at rest and during mental stress in men with isolated hypercholesterolemia (phenotype IIa; n = 21) or combined hyperlipidemia (phenotype IIb; n = 29), and age-matched normolipidemic controls (n = 41). The urinary excretion of 11-dehydrothromboxane B2 was elevated in patients compared to controls (IIa, p <0.05; IIb, p <0.001), and higher in type IIb than in IIa patients (p <0.05). Platelet secretion, assessed as plasma β-thromboglobulin levels, was higher in type IIb patients compared to controls (p <0.01) and type IIa patients (p <0.05) during mental stress. The urinary excretion of β-thromboglobulin was also elevated in type IIb patients compared to controls (p <0.05). Platelet aggregability at rest, as measured by filtragometry ex vivo was, however, reduced in both patient groups compared to controls (p <0.05). No correlations were found between plasma lipoprotein levels and markers of platelet function in vivo. Type IIb patients had higher plasma fibrinogen levels and higher leukocyte counts than controls (p <0.05 and p <0.001) and type IIa patients (p <0.05 and p = 0.06). Thromboxane excretion was positively related to fibrinogen levels and leukocyte counts (p <0.01 for both). Preliminary data regarding serum TNF-α also indicated an elevation of this inflammatory cytokine in type IIb patients (p <0.05 vs controls).In conclusion, thromboxane generation and platelet secretion in vivo are enhanced in patients with hypercholesterolemia, and particularly so among patients with concomitant elevation of plasma triglycerides. The mechanism is unknown, but inflammatory mediators may be involved. The present findings are of interest in relation to the role of triglycerides in coronary artery disease.

P-Selectin Enhances Generation of CD14+CD16+ Dendritic-Like Cells and Inhibits Macrophage Maturation from Human Peripheral Blood Monocytes

“…However, in atherosclerosis, monocytes may encounter P-selectin for a relatively long period of time, especially after extravasation, because P-selectin is also likely to be expressed on subluminal surface of inflammatory endothelium (55,56). In the circulating blood of patients with unstable atherosclerosis (57-60), stable coronary disease (4) and hypercholesterolemia (61,62), where activated platelets were found to be present, interaction of P-selectin with monocytes may last long enough to alter monocyte differentiation fate.…”

Platelet-Monocyte Complexes Support Monocyte Adhesion to Endothelium by Enhancing Secondary Tethering and Cluster Formation

“…12 These plateletleukocyte complexes are mostly considered markers of platelet-activating conditions and vessel wall disease, such as unstable atherosclerosis, 13,14 stable coronary disease, 15 and hypercholesterolemia. 16 Platelet activation was recently reported to induce the development of atherosclerotic lesions of carotid arteries in ApoE Ϫ/Ϫ mice by increasing the number of vessel wall-adhered leukocytes. 17 Furthermore, an earlier report suggested that platelets bound to monocytoid cells mediate increased adhesion to endothelial cells.…”

Platelets, atherothrombosis, and atherosclerosis

“…As discussed earlier, coronary artery, cerebrovascular, and peripheral artery disease are all associated with increased levels of activated platelets and serological markers of platelet activation. Known risk factors for atherosclerosis, such as hyperlipidemia 148 , hypertension 149 , diabetes mellitus 150 , and cigarette smoking 151 are associated with increased levels of activated platelets. Platelet activation as measured by P-selectin expression is associated with increased wall thickness of the carotid artery 152 and the progressive thickening of the carotid artery in patients with type II diabetes 153 .…”