Cx43 Response of Endothelial Cells to DHA is Not Mediated by the FFAR4

Abstract

The health of endothelial cells is important in the formation and progression of atherosclerotic plaques. These cells respond to factors circulating in the blood including free fatty acids (FFA). These FFA are linked to altered risk of cardiovascular diseases (CVD): saturated FFA increase whereas Omega3 polyunsaturated FFA decrease CVD risk. FFA structure may influence plaque growth by affecting the localized inflammatory response. Omega3 FFA bind to the FFA receptor 4 (FFAR4). As the health of the overlying endothelium is important in plaque formation, we were interested in the impact of Omega3 FFA docosahexaenoic acid (DHA) on endothelial cell (EC) inflammatory responses. Connexin 43 expression was evaluated as a marker of inflammation (Cx43 expression increases with inflammation). bEnd.3 cultured EC were treated with 30 uM DHA and protein isolated at 1.5, 3, 6, 12, 24, and 48 hrs along with a control at the same time. Whole cell protein was separated in a Western blot (equal loading), transferred to a membrane and probed for Cx43. EC response to DHA were time dependent: while EC Cx43 expression increased at 6 hrs, its expression had decreased by 24 hrs. At 24 hrs, blocking the FFAR4 receptor with AH‐7614 (5 uM) did not alter the DHA response. Interestingly, blocking the FFAR4 receptor decreased Cx43 expression at 24 hrs. Thus, the DHA induced decrease in Cx43 expression did not involve the FFAR4 receptor. The identity of the receptor mediating the Cx43 response to DHA may be the FFAR1 or could involves its conversion to prostaglandins.Support or Funding InformationGVSU Office of Undergraduate Research Student Summer ScholarsThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.