Circulating microparticles and endothelial progenitor cells in atherosclerosis: pharmacological effects of irbesartan

Abstract

Circulating microparticles and endothelial progenitor cells in atherosclerosis: pharmacological effects of irbesartan. J Thromb Haemost 2012; 10: 680-91.Summary. Aims: This study aimed to (i) employ our newly designed model, the hypertensive-hypercholesterolemic hamster (HH), in order to find out whether a correlation exists between circulating microparticles (MPs), endothelial progenitor cells (EPCs) and their contribution to vascular dysfunction and (ii) to assess the effect of irbesartan treatment on HH animals (HHI). Methods and Results: The results showed that compared with the control (C) group, HH displayed: (i) a significant increase in plasma cholesterol and triglyceride concentration, and an augmentation of systolic and diastolic arterial blood pressure, and of heart rate; (ii) a marked elevation of MPs and a significant decrease in EPCs; (iii) structural modifications of the arterial wall correlated with altered protein expression of MMP2, MMP9, MMP12, TIMP1, TIMP2 and collagen type I and III; (iv) a considerably altered reactivity of the arterial wall closely correlated with MPs and EPC adherence; and (v) an inflammatory process characterized by augmented expression of P-Selectin, E-Selectin, von Willebrand factor, tissue factor, IL-6, MCP-1 and RANTES. Additionally, the experiments showed the potential of irbesartan to correct all altered parameters in HH and to mobilize EPCs by NO, chemokines and adhesion molecule-dependent mechanisms. Conclusions: Hypertension associated with hypercholesterolemia is accompanied by structural modifications and expression of pro-inflammatory molecules by the vessel wall, the alteration of vascular tone, enhanced release of MPs and reduced EPCs; the ratio between the latter two may be considered as a marker of vascular dysfunction. Irbesartan, which exhibits a pharmacological control on the levels of MPs and EPCs, has the potential to restore homeostasis of the arterial wall.

Effects of Magnoline on P-Selectin's Expression in Diabetic Rats and its Reno-Protection

“…Literatures have reported that P-selectin is closely related to lipid metabolism disorders and atherosclerosis [31,32]. This study found that the inhibition of P-selectin expression by magnoline was associated with decreased blood lipids.…”

Hypercholesterolemia and Hypertension: Two Sides of the Same Coin

“…On the other hand, hypercholesterolemia was associated with vasa vasorum neovascularization, which is considered to be important in the progression of atherosclerotic disease. In another study in an animal model of atherosclerosis, Georgescu et al [38] showed that hypertension associated with hypercholesterolemia induced considerable changes consisting of lipid, collagen, and macrophage accumulation, activation of endothelial and smooth muscle cells, and synthesis of hyperplasic-multilayered basal lamina in the thoracic aortic arch and arteriole regions. Moreover, a considerably altered reactivity of the arterial wall was observed to be closely correlated with microparticles and endothelial progenitor cells adherence.…”

Enhancing endothelial progenitor cell for clinical use

“…Clinical studies documented a decreased number of circulating EPCs in coronary artery disease (CAD) patients, suggesting that levels of circulating EPCs might be associated with vascular endothelial function and cardiovascular risk factors [17][18][19][20][21] . Hill et al [10] measured colony-forming units of EPCs from patients with different degrees of cardiovascular risk but without history of cardiovascular disease.…”

“…It was also found that EPCs from subjects at high risk for cardiovascular events had higher rates of in vitro senescence than cells from subjects at low risk. Subsequently, it was demonstrated that reduced level of circulating EPCs independently predicts atherosclerotic disease progression and development of cardiovascular events [17][18][19] . Sen et al [17] , suggested that EPC determines the quality of the coronary collateral circulation.…”

“…Sen et al [17] , suggested that EPC determines the quality of the coronary collateral circulation. Georgescu et al [18] found that hypertension with hypercholesterolemia is accompanied by the alteration of vascular tone, the expression of proinflammatory molecules by the vessel wall, and reduced circulating EPC number. However, contrasting results were reported, by Güven et al [22] and Werner et al [23] , on the association between the level of circulating EPCs and severity of CAD.…”