Protective effect of tanshinone IIA against cardiac hypertrophy in spontaneously hypertensive rats through inhibiting the Cys-C/Wnt signaling pathway

Oncotarget. 2017 Feb 7;8(6):10161-10170. doi: 10.18632/oncotarget.14328.

Abstract

The study aimed to investigate the protective effect of tanshinone IIA against cardiac hypertrophy in spontaneously hypertensive rats (SHRs) through the Cys-C/Wnt signaling pathway. Thirty SHRs were randomly divided into cardiac hypertrophy, low- and high-dose tanshinone IIA groups. Ten Wistar-Kyoto rats were selected as control group. The systolic blood pressure (SBP), heart weight (HW), left ventricular weight (LVW) and body weight (BW) of all rats were recorded. HE staining and qRT-PCR were applied to observe the morphology of myocardial tissue and mRNA expressions of COL1A1 and COL3A1. ELISA and Western blotting were used to measure the serum asymmetric dimethylarginine (ADMA), nitric oxide (NO) and cardiac troponin I (cTnI) levels, and the expressions of the Cys-C/Wnt signaling pathway-related proteins, eNOS and Nox4. Compared with the cardiac hypertrophy group, the SBP, HW/BW, LVW/BW, swelling degree of myocardial cells, COL1A1 and COL3A1 mRNA expressions, serum cTnI and ADMA levels, and the Cys-C/Wnt signaling pathway-related proteins and Nox4 expressions in the low- and high-dose tanshinone IIA groups were decreased, but the endothelial NO synthase (eNOS), phosphorylated eNOS (Ser1177) and NO expressions were increased. No significant difference was found between the low- and high-dose tanshinone IIA groups. Our study indicated a protective effect of tanshinone IIA against cardiac hypertrophy in SHRs through inhibiting the Cys-C/Wnt signaling pathway.

Keywords: Cys-C/Wnt signaling pathway; cardiac hypertrophy; spontaneously hypertensive rats; tanshinone IIA.

MeSH terms

  • Abietanes / pharmacology*
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Cardiomegaly / genetics
  • Cardiomegaly / metabolism
  • Cardiomegaly / pathology
  • Cardiomegaly / prevention & control*
  • Cardiovascular Agents / pharmacology*
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Collagen Type III / genetics
  • Collagen Type III / metabolism
  • Cystatin C / metabolism*
  • Disease Models, Animal
  • Hypertension / drug therapy*
  • Hypertension / genetics
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Male
  • Myocardium / metabolism*
  • Myocardium / pathology
  • NADPH Oxidase 4 / metabolism
  • Nitric Oxide / blood
  • Nitric Oxide Synthase Type III / metabolism
  • Phosphorylation
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Time Factors
  • Troponin I / blood
  • Wnt Signaling Pathway / drug effects*

Substances

  • Abietanes
  • COL3A1 protein, rat
  • Cardiovascular Agents
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Collagen Type III
  • Cst3 protein, rat
  • Cystatin C
  • Troponin I
  • tanshinone
  • Nitric Oxide
  • N,N-dimethylarginine
  • Arginine
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • NADPH Oxidase 4
  • Nox4 protein, rat