Transport of Free Fatty Acids from Plasma to the Endothelium of Cardiac Muscle: A Theoretical Study.

Abstract

Fatty acids are transported in a multistep process from the plasma to the mitochondria, where they are oxidized in order to meet energy requirements of the myocardium. Some of those steps, mainly the crossing of the involved cells' membranes are far from being understood. Here, by means of mathematical modeling we address the problem of the fatty acid transport from the microvascular compartment to the endothelium. Values of parameters that are incorporated in the model are deduced from relevant experimental work. Concentration profiles are established as solutions of diffusion-reaction equations both numerically and using an analytical asymptotic approximation. The analytical solution accurately determines the fatty acid flux for any set of parameter values in contrast to off-the-shelf numerical solvers that fail under quite a few circumstances due to the stiffness of the differential equation system. Sensitivity analysis indicates that in spite of few uncertain parameter values, most of our conclusions are expected to be valid throughout the physiological range of operation. We find that in order to have an adequate fatty acid uptake rate it is essential for the luminal endothelial membrane to have very fast fatty acid transporters and/or specific sites that interact with the albumin-fatty acids complex.