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 TNFa,IL-6,IL-8,IFNg,IL-1b,ICAM1,VCAM1,E-selectin,laminin B,and vimentin was documented in both ECs.The promoter hypomethylation of various key inflammatory cytokines(TNFa,IL-6,and IL-8),integrin(ICAM1)associated with leukocyte transendothelial migration,and extracellular matrix genes(vimentin,and laminin)were also observed.Further,the in-vitro data was in accordance with ex-vivo 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.