The effect of n−3 fatty acids on coronary atherosclerosis: Results from SCIMO, an angiographic study, background and implications
According to the model of “response to injury”, the arterial endothelium is occasionally injured in hyperlipidemia, hypertension, diabetes mellitus and in other states known as risk factors. The ensuing inflammatory response is modulated by cytokines and growth factors, among them platelet-derived growth factor (PDGF), and monocyte chemoattractant protein-1 (MCP-1). In two independent studies, we demonstrated that mRNA levels for PDGF-A and-B and for MCP-1 are reduced after ingestion of n−3 fatty acids by human volunteers. This reduction persists after monocyte stimulation/differentiation by adherence. Moreover, the reduction is brought about only by dietary n−3 fatty acids and not by other calsses of unsaturated fatty acids (n−6 or n−9). This appears to be one major mechanism of action of reduced progression/increased regression of establihed coronary artery disease by ingestion of 1.5 g/d n−3 fatty acids, as assessed by coronary angiography in a randomized placebo-controlled double-blind intervention study in 223 patients. The study was conducted according to “Good Clinical Practice”, comprehensive rules regulating investigations with pharmaceutical compounds. Together, our investigations lend support to the importance of PDGF-A, PDGF-B, and MCP-1 in the pathogenesis of atherosclerosis, and the beneficial role of n−3 fatty acids therein.