Abstract

Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in drug development for treating cancer. Several studies performed in the cardiovascular field on TSP-1 are contradictory, the role of TSP-1 in the physiopathology of cardiovascular disorders (CVDs) being, for the moment, incompletely understood and may be due to the presence of several domains in its structure which can stimulate many cellular receptors. It has been reported to inhibit NO-mediated signaling and to act on the angiogenesis, tissue perfusion, endothelial cell proliferation, and homeostasis, so we aimed to quantify the effect Perindopril has on TSP-1 plasma levels in hypertensive patients with endothelial dysfunction in comparison with other antihypertensive drugs, such as beta blockers, calcium channel blockers, and diuretics, in a chronic treatment. As a conclusion, patients under treatment with Perindopril had increased plasma levels of TSP-1 compared with other hypertensive patients and with the control group. The results of this study confirms the pleiotropic properties of Perindopril: anti-proliferative, anti-inflammatory, with effects showed by quantifying a single biomarker: TSP-1.

Highlights

  • Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in the drug development for treating cancer

  • TSP-1 is the most studied member of the family of thrombospondins, a family which consists of five multimeric, multidomain calcium-binding glycoproteins that act as regulators of cell-cell and cell-matrix associations, which interact with other extracellular matrix molecules that can influence their function [5]

  • This has been classified as a counter-adhesive protein that is capable of interacting with various cell-surface receptors, growth factors, bioactive molecules, proteases, and several studies have shown its implications in the pathogenesis of many cardiovascular diseases [2,13,14,15,16,17,18,19]

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Summary

Introduction

Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in the drug development for treating cancer. Studies showed that it inhibits NO-mediated signaling It acts on angiogenesis, tissues perfusion, endothelial cell proliferation, and homeostasis [1,2,3,4]. Being constitutively present within the blood vessels, it interacts with many important proteins that are involved in maintaining homeostasis and the vascular structure This has been classified as a counter-adhesive protein that is capable of interacting with various cell-surface receptors, growth factors, bioactive molecules, proteases, and several studies have shown its implications in the pathogenesis of many cardiovascular diseases [2,13,14,15,16,17,18,19]

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