In:
Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 8, No. 1 ( 2019-01-08)
Abstract:
Cardiac fibrosis is a core pathological process associated with heart failure. The recruitment and differentiation of primitive fibroblast precursor cells of bone marrow origin play a critical role in pathological interstitial cardiac fibrosis. The K C a 3.1 channels are expressed in both ventricular fibroblasts and circulating mononuclear cells in rats and are upregulated by angiotensin II . We hypothesized that K C a 3.1 channels mediate the inflammatory microenvironment in the heart, promoting the infiltrated bone marrow–derived circulating mononuclear cells to differentiate into myofibroblasts, leading to myocardial fibrosis. Methods and Results We established a cardiac fibrosis model in rats by infusing angiotensin II to evaluate the impact of the specific K C a 3.1 channel blocker TRAM ‐34 on cardiac fibrosis. At the same time, mouse CD 4 + T cells and rat circulating mononuclear cells were separated to investigate the underlying mechanism of the TRAM ‐34 anti–cardiac fibrosis effect. TRAM ‐34 significantly attenuated cardiac fibrosis and the inflammatory reaction and reduced the number of fibroblast precursor cells and myofibroblasts. Inhibition of K C a 3.1 channels suppressed angiotensin II –stimulated expression and secretion of interleukin‐4 and interleukin‐13 in CD 4 + T cells and interleukin‐4– or interleukin‐13–induced differentiation of monocytes into fibrocytes. Conclusions K C a 3.1 channels facilitate myocardial inflammation and the differentiation of bone marrow‐derived monocytes into myofibroblasts in cardiac fibrosis caused by angiotensin II infusion.
Type of Medium:
Online Resource
ISSN:
2047-9980
DOI:
10.1161/JAHA.118.010418
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2019
detail.hit.zdb_id:
2653953-6
