Abstract
Background C-reactive protein (CRP) is an independent biomarker of systemic inflammation and a predictor of future cardiovascular disease (CVD). More than just a pure bystander, CRP directly interacts with endothelial cells to decrease endothelial nitric oxide synthase (eNOS) expression and bioactivity, decrease nitric oxide (NO) production, and increase the release of vasoconstrictors and adhesion molecules. Race is significantly associated with CRP levels and CVD risks. With aerobic exercise, the vessel wall is exposed to chronic high laminar shear stress (HiLSS) that shifts the endothelium phenotype towards an anti-inflammatory, antioxidant, antiapoptotic, and antiproliferative environment. Thus, the purpose of this study was to assess the racial differences concerning the CRP-induced effects in endothelial cells and the potential role of HiLSS in mitigating these differences. Methods Human umbilical vein endothelial cells (HUVECs) from four African American (AA) and four Caucasian (CA) donors were cultured and incubated under the following conditions: (1) static control, (2) CRP (10 μg/mL, 24 hours), (3) CRP receptor (FcγRIIB) inhibitor followed by CRP stimulation, (4) HiLSS (20 dyne/cm2, 24 hours), and (5) HiLSS followed by CRP stimulation. Results AA HUVECs had significantly higher FcγRIIB receptor expression under both basal and CRP incubation conditions. Blocking FcγRIIB receptor significantly attenuated the CRP-induced decrements in eNOS expression only in AA HUVECs. Finally, HiLSS significantly counteracted CRP-induced effects. Conclusion Understanding potential racial differences in endothelial function is important to improve CVD prevention. Our results shed light on FcγRIIB receptor as a potential contributor to racial differences in endothelial function in AA.
Highlights
Endothelial dysfunction plays an integral role in the progression of cardiovascular disease (CVD) and is characterized by a reduction in nitric oxide (NO) that promotes a proinflammatory and proatherogenic environment [1,2,3,4]
Within each racial group, applying high laminar shear stress (HiLSS) prior to C-reactive protein (CRP) incubation resulted in the greatest attenuation of CRP induced effects on endothelial nitric oxide synthase (eNOS) (Figure 2, CA: p < 0:01, AA: p < 0:005)
Only HiLSS condition resulted in higher production in NOx in the culture media in AA compared to CA (Figure 3, p < 0:05)
Summary
Endothelial dysfunction plays an integral role in the progression of cardiovascular disease (CVD) and is characterized by a reduction in nitric oxide (NO) that promotes a proinflammatory and proatherogenic environment [1,2,3,4]. The elevated levels of systemic inflammation and endothelial dysfunction observed in AAs compared to CAs may contribute to the higher prevalence of cardiovascular risk factors and the pathogenesis of HT in this population. Several large-scale studies, including the Dallas Heart Study, have reported racial differences in plasma C-reactive protein (CRP) levels, with AA exhibiting significantly higher median CRP levels compared to CA [7]. Current evidence has demonstrated that plasma CRP level is a prognostic biomarker of CVD and has a direct effect on endothelial cells (ECs) by reducing endothelial NO synthase (eNOS) mRNA and protein expression necessary for NO. AA HUVECs had significantly higher FcγRIIB receptor expression under both basal and CRP incubation conditions.
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