Anti-endothelial cell antibody rich sera from rheumatic heart disease patients induces proinflammatory phenotype and methylation alteration in endothelial cells.

Rheumatic heart disease (RHD) is a major cause of cardiovascular morbidity and mortality in developing nations like India. RHD commonly affects the mitral valve which is lined by a single layer of endothelial cells (ECs). The role of ECs in mitral valve damage during RHD is not well elucidated. In here, anti-endothelial cell antibody from RHD patients has been used to stimulate the ECs (HUVECs and HMVECs). ECs proinflammatory phenotype with increased expression of TNFα, IL-6, IL-8, IFNγ, IL-1β, ICAM1, VCAM1, E-selectin, laminin B, and vimentin was documented in both ECs. The promoter hypomethylation of various key inflammatory cytokines (TNFα, IL-6, and IL-8), integrin (ICAM1) associated with leukocyte transendothelial migration, and extracellular matrix genes (vimentin, and laminin) were also observed. Further, the data was in accordance with observations which correlated significantly with the etiological factors such as smoking, socioeconomic status, and housing. Thus, the study sheds light on the role of ECs in RHD which is a step forward in the elucidation of disease pathogenesis.