Direct effects of long-chain non-esterified fatty acids on vascular cells and their relevance to macrovascular complications of diabetes

Diabetes leads to a marked increase in cardiovascular disease caused by atherosclerosis. Cardiovascular complications of diabetes are associated with lipid abnormalities, mainly manifested as elevated levels of triglycerides. Hydrolysis of triglycerides by lipases in the arterial wall is believed to cause increased levels of non-esterified fatty acids (NEFAs) in lesions of atherosclerosis. Recent research has shown that long-chain NEFAs have a multitude of direct effects on cell types involved in atherogenesis. Thus, some of the most common long-chained fatty acids present in triglycerides, oleic acid and linoleic acid, have been shown to induce adhesion molecule expression, cytokine expression and apoptosis in endothelial cells, to increase cholesterol uptake and reduce cholesterol efflux in macrophages, and to increase arterial smooth muscle cell proliferation and migration. Certain NEFAs liberated from triglycerides may therefore play an important role in accelerating atherosclerosis caused by diabetes by directly affecting the key cell types involved in atherogenesis.