CC-chemokine Receptor7and Its Ligand CCL19Promotes Mitral Valve Interstitial Cell Migration And Repair

Objectives To explore the role of CCL19/CCR7axis in rheumatic mitral stenosis bycharacterizing the expression of CCL19and CCR7in human mitral valves fromrheumatic mitral stenosis (RMS) and examining their effects on the proliferation andwound repair of human mitral valve interstitial cells (MVICs). Methods Part one:Collected the RMS diseased valve tissue from valve replacement surgery and normalvalve tissue, Observed lesions valve tissue pathological by Hematoxylin and eosinstaining(HE Staining), and detected CCL19and CCR7expression of mitral valvetissues by inmmunohistochemical staining. Part two: Isolated andcultured human mitral valve interstitial cells with primary cell culture techniques,Analysis CCR7expression of MVICs by inmmunofluorescence staining, StimulatedMVICs with different concentrations of CCL19, Used the MTS cell proliferation kitand scratch wound experiment to assess the CCL19combination with CCR7effect onMVICs proliferation and wound repair. Result Part one: HE staining showed that cellfibers arranged messy, interstitial cell hyperplasia was significantly associated withneovascularization and inflammatory cell invasion in the diseased valve tissue ofRMS. Immunohistochemocal staining showed that CCL19and CCR7high expressedin the diseased valve tissue of RMS, and CCL19is mainly distributed in theinflammatory cell area, while CCR7mainly expression of the interstitial cells of thevalve, but the normal valve tissue did not express CCL19and CCR7. Part two:Immumoflurescence staining confirmed that the R-MVIC（sRMS MVICs，R-MVICs）expressed CCR7, and Treatment with CCL19could not increase significantly their CCR7expression. N-MVICs（normal MVICs，N-MVICs） did not express CCR7,After used CCL19treatment, the N-MVICs was the low expression of CCR7, but nosignificant concentration-dependent. MTS cell proliferation assay showed thatCCL19do not effect on proliferation of MVICs, Scratch experiments showed thatCCL19treated MVICs, can significantly promote its migration and the effect can beblocked with anti-CCR7neutralizing antibody. Conclusion RMS diseased valvetissue pathological changes to the performance of tissue remodeling, thickening,angiogenesis and inflammatory cell invasion, CCL19and CCR7were high expressedin RMS diseased heart valves, and CCL19was mainly expressed in the invasion ofinflammatory cells, CCR7expressed in invalvular interstitial cells, both of which didnot express in normal valve tissue. R-MVICs expression of CCR7, CCL19canactivate N-MVICs expression of CCR7, Stimulating MVICs with CCL19canpromote migration and wound repair, but had no effect on cell proliferatio n.