title: Angiotensin II increases secreted frizzled-related protein 5 (sFRP5) expression through AT1 receptor/Rho/ROCK1/JNK signaling in cardiomyocytes.
abstract: Secreted frizzled-related protein 5 (sFRP5) is a novel adipokine that functions as an inhibitor of Wnt signaling and is involved in embryonic development, proliferation, atherosclerosis, and apoptosis. Studies have shown that sFRP1-4 is expressed in cardiomyocytes, and sFRP3 and sFRP4 are elevated during heart failure. However, it is unclear whether sFRP5 is expressed in cardiomyocytes or cardiac hypertrophy, and as regards the effects of sFRP5 in the process. Here, we report the expression and the corresponding mechanisms of sFRP5 in angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. Neonatal rat ventricular myocytes were exposed to increasing concentrations of Ang II for 12-72 h. Y27632 was used to block ROCK signal. PD98059, SB203580, and SP600125 were used to inhibit ERK1/2, p38 MAPK, and JNK signaling pathways, respectively, and anisomycin was used to activate JNK pathway. RT-PCR and Western-blot determined the expressions of sFRP5. BNP, TNF-α, ROCK1, ROCK2, MYPT1, and JNK were examined through Western-blot analysis. Ang II increased sFRP5 mRNA and protein levels in a time- and dose-dependent manner. Telmisartan, Y27632 and SP600125 effectively suppressed the expression of sFRP5. sFRP5 downregulated BNP and TNF-α expressions in hypertrophic cardiomyocytes. sFRP5 is expressed in cardiomyocytes, and upregulated in Ang II-induced cardiomyocyte hypertrophy through the AT1 receptor/Rho/ROCK1/JNK signaling pathway. sFRP5 may play an important role during cardiomyocyte hypertrophy.
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
authors.forename: Bingyan
authors.initials: B
authors.lastname: Guo
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Miao
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
authors.forename: Suyun
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China. lyjbs2009@yeah.net.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Li
mesh_terms: D054392:Adipokines / Q000235:genetics* / Q000378:metabolism*; D000577:Amides / Q000494:pharmacology; D000804:Angiotensin II / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D054392:Adipokines; D000577:Amides; D000804:Angiotensin II; D005136:Eye Proteins; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C000608752:sFRP5 protein, rat; D000094742:Secreted Frizzled-Related Proteins; C108830:Y 27632
keywords: Adipokine; Angiotensin II; Cardiomyocyte; Hypertrophy; Secreted frizzled-related protein 5