RGD Reference Report - KCa3.1 Channels Promote Cardiac Fibrosis Through Mediating Inflammation and Differentiation of Monocytes Into Myofibroblasts in Angiotensin II -Treated Rats.

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KCa3.1 Channels Promote Cardiac Fibrosis Through Mediating Inflammation and Differentiation of Monocytes Into Myofibroblasts in Angiotensin II -Treated Rats.
Authors:	She, Gang Ren, Yu-Jie Wang, Yan Hou, Meng-Chen Wang, Hui-Fang Gou, Wei Lai, Bao-Chang Lei, Ting Du, Xiao-Jun Deng, Xiu-Ling
Citation:	She G, etal., J Am Heart Assoc. 2019 Jan 8;8(1):e010418. doi: 10.1161/JAHA.118.010418.
RGD ID:	401700380
Pubmed:	PMID:30563389 (View Abstract at PubMed)
PMCID:	PMC6405723 (View Article at PubMed Central)
DOI:	DOI:10.1161/JAHA.118.010418 (Journal Full-text)
Background 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 KCa3.1 channels are expressed in both ventricular fibroblasts and circulating mononuclear cells in rats and are upregulated by angiotensin II . We hypothesized that KCa3.1 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 KCa3.1 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 KCa3.1 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 KCa3.1 channels facilitate myocardial inflammation and the differentiation of bone marrow-derived monocytes into myofibroblasts in cardiac fibrosis caused by angiotensin II infusion.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
KCNN4	Human	Cardiac Fibrosis	ameliorates	ISO	Kcnn4 (Rattus norvegicus)		RGD
Kcnn4	Rat	Cardiac Fibrosis	ameliorates	IMP			RGD
Kcnn4	Mouse	Cardiac Fibrosis	ameliorates	ISO	Kcnn4 (Rattus norvegicus)		RGD

Objects Annotated

Genes (Rattus norvegicus)

Kcnn4 (potassium calcium-activated channel subfamily N member 4)

Genes (Mus musculus)

Kcnn4 (potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4)

Genes (Homo sapiens)

KCNN4 (potassium calcium-activated channel subfamily N member 4)

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KCa3.1 Channels Promote Cardiac Fibrosis Through Mediating Inflammation and Differentiation of Monocytes Into Myofibroblasts in Angiotensin II -Treated Rats.