Testosterone as a protective factor against atherosclerosis--immunomodulation and influence upon plaque development and stability

Abstract

Inflammation plays a central pathogenic role in the initiation and progression of coronary atheroma and its clinical consequences. Cytokines are the mediators of cellular inflammation and promote local inflammation in the arterial wall, which may lead to vascular smooth muscle apoptosis, degradation of the fibrin cap and plaque rupture. Platelet adhesion and thrombus formation then occur, resulting clinically in unstable angina or myocardial infarction. Recent studies have suggested that cytokines are pathogenic, contributing directly to the disease process. 'Anti-cytokine' therapy may, therefore, be of benefit in preventing or slowing the progression of cardiovascular disease. Both oestrogens and testosterone have been shown to have immune-modulating effects; testosterone in particular appears to suppress activation of pro-inflammatory cytokines. Men with low testosterone levels are at increased risk of coronary artery disease. An anti-inflammatory effect of normal physiological levels of sex hormones may, therefore, be important in atheroprotection. In this Article, we discuss some of the mechanisms involved in atherosclerotic coronary artery disease and the putative link between testosterone deficiency and atheroma formation. We present the hypothesis that the immune-modulating properties of testosterone may be important in inhibiting atheroma formation and progression to acute coronary syndrome.