Aortic mitochondrial synthesis of lipid and its response to cholesterol feeding.

The rates and products of lipid synthesis from acetate-I-14C were studied in mitochondria isolated from control and atherosclerotic rabbit aorta. More acetate was incorporated into fatty acids in the cholesterol-fed animals. The mechanism was one of chain elongation, and the resultant products were longer in chain length. The newly elongated fatty acids were esterified mostly into phospholipids, presumably those turning over most rapidly. A hypothesis is proposed for the pathogenetic sequence: Cholesterol feeding alters transport functions of the mitochondrial membranes of aortic smooth muscle cells. Respiration and redox state are altered and consequently acetate is incorporated more rapidly into fatty acids as an alternate mechanism for oxidation of the reduced form of nicotin-amide-adenine dinucleotide (NADH). Rapidly turning over phospholipids esterify these fatty acids and may transfer them ultimately to cholesterol. Esterified cholesterol is less exchangeable and commences to accumulate.