LOX-1 and its Implications on Cardiovascular Diseases a Possible New Perspective Target on Atherosclerosis

Gorga Elio

doi:10.4172/2155-9880.1000232

Abstract

The receptor for oxidized low density lipoprotein (LOX-1), encoded by the gene ORL1, is a scavenger receptor that plays a key role in the pathogenesis of atherosclerosis. The activation of LOX-1 is associated with apoptosis of endothelial cells, smooth muscle cells and macrophages. This process is an important mechanism in atherosclerotic plaque destabilization and thus in the development of acute coronary syndromes. Genetic association of independent studies have associated variants of the gene ORL1 a different susceptibility to myocardial infarction. These polymorphisms (SNPs) are located in intronic sequences of the gene OLR1 and regulate the expression of a new isoform of splicing, the LOXIN characterized by the lack of exon 5. It is able to counter cytotoxicity induced by Ox-LDL by reducing the degree of apoptosis by 40%.

Highlights

Atherosclerosis is characterized by the accumulation of lipids and fibrous elements in the arteries, and is the most important contributor to the growing burden of cardiovascular diseases
Our study identifies and characterizes the direct interaction between LOX-1 and C reactive protein (CRP) and suggests that this interaction may mediate CRPinduced endothelial dysfunction [17]
Flow cytometry and immunofluorescence studies have shown that the new isoform Loxin can reduce the cytotoxicity induced by ox-LDL, reducing them by 40% degree of apoptosis

Summary

Introduction

Atherosclerosis is characterized by the accumulation of lipids and fibrous elements in the arteries, and is the most important contributor to the growing burden of cardiovascular diseases. The major risk factors of atherosclerosis, such as hypertension, diabetes, smoking and free radicals, have been known to induce endothelial dysfunction. It has been suggested that others “non traditional” risk factors, such oxidative modification of LDL (ox LDL), have an important rule on atherosclerosis [1] development. Oxidized low-density lipoprotein, acting on their receptor (Lectin-like oxidized low density lipoprotein receptor-1, LOX-1), induce endothelial dysfunction [2]. Transgenic mouse models for LOX-1 over expression or gene knockout suggests that LOX-1 contributes to atherosclerotic plaque formation and progression. LOX-1 activation by oxidized LDL (low-density lipoprotein) binding stimulates intracellular signaling, gene expression and production of superoxide radicals

Role of LDL in the Pathogenesis of Atherosclerosis

Findings

Conclusion