Exaggerated myocardial oxLDL amount and LOX-1 receptor over-expression associated with coronary microvessel inflammation in unstable angina

Abstract The pathophysiological relationship between coronary atherosclerosis and coronary microvessels remains undefined and the specific causative role of oxidatively modified low density lipoprotein (oxLDL) in human atherosclerosis is debated. The purposes of this study are to investigate whether coronary microvessels are involved in coronary atherosclerosis and whether oxLDL is injurious to coronary microvessel. A combination of immunohistochemical, RT-PCR and real time-PCR studies performed on myocardial biopsy specimens from patients with mitral stenosis (control hearts, CHs) and from unstable and stable angina patients (UAP and SAP), demonstrated that oxLDL was associated with a chronic low grade inflammation in SAP and with a severe high grade inflammation in UAP. The grade of inflammation was correlated with the amount of oxLDL in endothelial cells and macrophages. OxLDL amount was notably higher in UAP than in SAP . The marked amount of oxLDL in UAP and the interaction of oxLDL with lectin-like oxLDL (LOX-1) receptor overcame the repressive capacity of transcriptional factor octamere 1 (OCT-1) with consequent activation of a series of inflammatory endothelial feedback mechanisms resulting in LOX-1 gene overexpression, endothelial inflammation as well as uncontrolled nuclear factor kappa B (NFkB) activation. Moreover, genes for signal transducer and activator transcriptional factor 1α (STAT1α) and numerous proinflammatory cytokines were overexpressed. The present results may have pathophysiological and clinical significance because they suggest that coronary atherosclerosis is a disease not confined to the large arteries but involving the whole coronary tree, and oxLDL plays a major role in the activation of microvessel inflammation.