CC-chemokine receptor 7 and its ligand CCL19 promote mitral valve interstitial cell migration and repair.

Wang Xiaozhi,Miao Liping,Wu Yanhu,Kong Xiangqing,Zhao Rong,Wang Liang

doi:10.7555/jbr.29.20150031

Wang Xiaozhi, Miao Liping + Show 4 more

Open Access

https://doi.org/10.7555/jbr.29.20150031

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Abstract

The effect of CC-chemokine receptor 7 (CCR7) and CC-chemokine ligand 19 (CCL19) on rheumatic mitral stenosis is unknown. This study aimed to explore the roles of CCR7 and CCL19 in rheumatic mitral stenosis by measuring the expression of CCR7 and CCL19 in human mitral valves from rheumatic mitral stenosis patients. Additionally, we examined their effects on human mitral valve interstitial cells (hMVICs) proliferation, apoptosis and wound repair. CCR7 and CCL19 expression was measured in the mitral valves from rheumatic mitral stenosis patients (n = 10) and compared to normal mitral valves (n = 5). CCR7 was measured in cultured hMVICs from rheumatic mitral stenosis patients and normal donors by RT-PCR and immunofluorescence. The cells were also treated with exogenous CCL19, and the effects on wound healing, proliferation and apoptosis were assayed. In the rheumatic mitral valves, valve interstitial cells expressed CCR7, while mononuclear cells and the endothelium expressed CCL19. Healthy mitral valves did not stain positive for CCR7 or CCL19. CCR7 was also detected in cultured rheumatic hMVICs or in normal hMVICs treated with CCL19. In a wound healing experiment, wound closure rates of both rheumatic and normal hMVICs were significantly accelerated by CCL19. These effects were abrogated by a CCR7 neutralizing antibody. The CCR7/CCL19 axis did not influence the proliferation or apoptosis of hMVICs, indicating that wound healing was due to increased migration rates rather than increased proliferation. In conclusion, CCR7 and CCL19 were expressed in rheumatic mitral valves. The CCR7/CCL19 axis may regulate remodeling of rheumatic valve injury through promoting migratory ability of hMVICs.

Highlights

The prevalence of rheumatic fever has greatly decreased in developed countries, the late sequelae of rheumatic fever, rheumatic mitral stenosis, still results in high morbidity and mortality in developing countries[1]
Since significant lymphocyte infiltration occurs during all the stages of rheumatic mitral stenosis[12,13], we hypothesized that chemokine receptor 7 (CCR7) and CC-chemokine ligand 19 (CCL19) may regulate the pathological behavior of human mitral valve interstitial cells, which are involved in chronic remodeling of stenotic mitral valves
We investigated the expression of CCR7 and CCL19 in rheumatic mitral stenosis mitral valves and whether the CRR7/CCL19 axis mediated human mitral valve interstitial cells (hMVICs) function

Summary

Introduction

The prevalence of rheumatic fever has greatly decreased in developed countries, the late sequelae of rheumatic fever, rheumatic mitral stenosis, still results in high morbidity and mortality in developing countries[1]. In response to rheumatic fever, an autoimmune response in the mitral valve damages the endothelial layer, which triggers a subsequent inflammatory response that involves neovascugThese authors contributed to this work. Valve interstitial cells are both fibroblasts and myofibroblasts, and are very important in control of heart valve homeostasis and diseased valve repair or remodeling[10,11]. Since significant lymphocyte infiltration occurs during all the stages of rheumatic mitral stenosis[12,13], we hypothesized that CCR7 and CCL19 may regulate the pathological behavior of human mitral valve interstitial cells (hMVICs), which are involved in chronic remodeling of stenotic mitral valves. We investigated the expression of CCR7 and CCL19 in rheumatic mitral stenosis mitral valves and whether the CRR7/CCL19 axis mediated hMVIC function

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