Lipid metabolism in the ischemic and reperfused heart

Abstract

Proper functioning of the heart depends, among others, on an unimpeded supply of molecular oxygen. The oxygen is used for the oxidation of substrates, mainly glucose and fatty acids, in the mitochondrial matrix. Fatty acids are supplied to the heart from the blood compartment, either complexed to albumin or esterified in triacylglycerol-containing lipoproteins, such as chylomicrons and very low density lipoproteins (Fig. 1). In addition to serving as substrates in oxidative metabolic processes, fatty acids are incorporated in phospholipids, important building blocks of cellular membranes, and in triacylglycerols, the intracellular store of fatty acids. A minor part of fatty acids, in particular arachidonic acid, serves as precursor of biological active compounds [1]. Recent findings strongly suggest that fatty acids themselves can exert regulating effects on ion transport and gene expression in parenchymal cells [2]. Prior to transport through the endothelial cells (via an incompletely understood mechanism), fatty acids are released from the albumin-fatty acid complex or hydrolysed from the triacylglycerol core of the circulating lipoproteins by lipoprotein lipase (Fig. 1). The latter enzyme is attached to the luminal side of the endothelial membrane. After albumin-mediated diffusion through the interstitial space, fatty acids are transferred across the sarcolemma of the cardiomyocytes by diffusion through the lipid bilayer and/or via a protein-mediated transport mechanism [1]. At present, at least three different proteins have been suggested for a role in transmembrane trafficking of fatty acyl moieties [3].