Racial Differences in Fc gamma Receptor Expression and Shear Stress Response to CRP in Endothelial Cells
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C-reactive protein (CRP) is a robust and independent marker of inflammation. It also decreases endothelial nitric oxide synthase (eNOS) expression and bioactivity, increases vasoconstrictor release, and increases adhesion molecule expression. African Americans (AA) have higher levels of CRP than Caucasians (CA), and CRP was found to cause a greater reduction in eNOS expression and bioactivity in the AA endothelial cells (ECs) compared with CA. In addition, AA ECs have shown larger improvements in EC health in response to the exercise mimetic, high levels of laminar shear stress (HiLSS). CRP mediates the biological effects in ECs via Fcγ receptors. CRP binding to Fcγ receptors inhibits eNOS activation via Protein Phosphatase 2A (PP2A), a down-stream protein that dephosphorylates eNOS rendering it inactive. Preliminary data from the doctoral candidate shows racial differences in the expression of PP2A with CRP incubation. The current study used an in vitro cell model to investigate how CRP may differentially affect ECs from AA and CA donors and whether HiLSS eliminates racial differences in CRP-induced proinflammatory and proatherogenic effects. Major findings of this study are: 1) CRP induced racial differences in eNOS expression and activity, NO bioavailability, ET-1 release, and expression of adhesion molecules; 2) CRP receptors (FcγRIIB) have higher levels of expression in AA ECs than in CA ECs under basal conditions and after CRP incubation, which partially contributed to the CRP-induced racial differences; 3) The exercise mimetic, HiLSS, counterbalanced the antagonistic effects of CRP, eliminated racial differences in suppressed eNOS expression and bioactivity, reduced NO bioavailability, and increased ET-1 release and adhesion molecules after CRP pre-incubation. The significance of this current study provides a better understanding of the cellular mechanism of racial differences in endothelial dysfunction. This study provides evidence that HiLSS is effective in reversing the proinflammatory and proatherogenic effects induced by CRP and thereby eliminating the racial differences. Most importantly, this study is targeted to a high-risk population and provides evidence that exercise is particularly beneficial to the vascular function of AA.