THE PROATHEROGENIC ROLE OF THE TRPV4 CALCIUM-PERMEABLE CHANNEL IN MACROPHAGES

Abstract

Atherosclerosis is a multi-faceted chronic disease and one of the leading causes of cardiovascular diseases which attribute to 28.2% of all-cause mortality worldwide. Central tenets of atherogenesis are macrophage passage and transformation to foam cells. It is known that numerous macrophage membrane proteins regulate this process by controlling properties such as migration and binding and uptake of oxidized lipids. The focus of this study is to identify mechanisms by which the transient receptor potential (TRP) channel of the vanilloid subfamily, TRPV4, a calcium-permeable channel, regulates proatherogenic macrophage functions. The findings show TRPV4 is expressed and functional in macrophages, TRPV4 modulates macrophage migratory characteristics, oxidized low-density lipoprotein (oxLDL) uptake and foam cell formation is reliant on TRPV4-elicited Ca2+ influx, and the physiological inflammatory stimulus of lipopolysaccharide can mediate TRPV4 function. These results identified previously unknown components to macrophage migration and foam cell development. Collectively, these discoveries associate the TRPV4 channel with atherogenesis by identifying new regulators for macrophage phagocytosis and migration that are essential to atherosclerosis development.