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Association Between Soluble Epoxide Hydrolase and TRPC3 Channels in Pathological Cardiac Hypertrophy
Author(s) -
Zhou Yang,
Sun WenTao,
Xue HongMei,
He GuoWei,
Yang Qin
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02697
Subject(s) - epoxide hydrolase 2 , trpc3 , homocysteine , muscle hypertrophy , medicine , endocrinology , myocyte , chemistry , biology , biochemistry , receptor , transient receptor potential channel , enzyme , trpc
Objectives Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Although previous studies have shown a positive correlation between homocysteine levels and the incidence of cardiac hypertrophy and remodeling, the molecular mechanisms by which homocysteine promotes the development of cardiac hypertrophy remain inadequately understood. In this study, we investigated the role of soluble epoxide hydrolase (sEH) and transient receptor potential isoform 3 (TRPC3) channels in homocysteine‐induced cardiac hypertrophy with further elucidating the association between sEH and TRPC3. Methods H9c2 cardiomyocytes were exposed to different concentrations of homocysteine ranging from 25 to 200 μmol/L for different duration. The cell surface area was measured by phase contrast microscope and image analysis software. The mRNA and protein expressions of sEH, TRPC3 channels, and hypertrophic markers beta‐smooth muscle myosin heavy chain (β‐MHC) and atrial natriuretic peptide (ANP) were detected by quantitative polymerase chain reaction and western blot. Results Homocysteine treatment dose‐dependently and time‐dependently increased the expression of β‐MHC and ANP in H9c2 cardiomyocytes. Both mRNA and protein levels of sEH and TRPC3 channels were unregulated by homocysteine. Inhibition of sEH with 1‐trifluoromethoxyphenyl‐3‐(1‐propionylpiperidin‐4‐yl) urea (TPPU) significantly suppressed homocysteine‐induced upregulation of β‐MHC and ANP and attenuated the increase of cell size. Pyr3, a selective TRPC3 channel blocker, also exerted a strong anti‐hypertrophic effect against homocysteine. Treatment with TPPU significantly suppressed the expression of TRPC3 channels in homocysteine‐exposed H9c2 cells. Conclusions: Both sEH and TRPC3 channels are involved in homocysteine‐induced hypertrophy of cardiomyocytes. TRPC3 channels may act as a downstream mediator for sEH activation induced by homocysteine to promote cardiac hypertrophy.