title: CC-chemokine receptor 7 and its ligand CCL19 promote mitral valve interstitial cell migration and repair.
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.
authors.affiliation: Department of Cardiology.
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology.
authors.forename: Liping
authors.initials: L
authors.lastname: Miao
authors.affiliation: Department of Cardiology.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Nanjing Medical University , Nanjing, Jiangsu 210029 , China .
authors.forename: Yanhu
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Cardiology.
authors.forename: Xiangqing
authors.initials: X
authors.lastname: Kong
keywords: CC-chemokine ligand 19; CC-chemokine receptor 7; migration; rheumatic mitral stenosis; wound repair