Association of decreased serum vasostatin-2 level with ischemic chronic heart failure and with MACE in 3-year follow-up: Vasostatin-2 prevents heart failure in myocardial infarction rats

Int J Cardiol. 2016 Oct 15:221:1-11. doi: 10.1016/j.ijcard.2016.06.065. Epub 2016 Jun 25.

Abstract

Background: We investigated whether serum vasostatin-2 level is related to chronic heart failure (CHF) in patients with previous myocardial infarction (MI) and MACE in 3-year follow-up. The biological effect of vasostatin-2 on ischemic HF was evaluated in animal experiments.

Methods: After exclusion of the subjects not eligible, this study included 450 patients with CHF and previous MI, and 149 healthy controls. Serum vasostatin-2 level was analyzed. CHF patients were followed up for three years and major adverse cardiac events (MACE) were recorded, defined as reinfarction, target-vessel revascularization, cardiovascular death and refractory HF requiring hospitalizations.

Results: Notably, serum vasostatin-2 level was decreased in CHF patients than in controls, and significant difference was observed between CHF patients with MACE and those without (both P<0.05). Vasostatin-2 level was correlated with HF stages (Spearman's r=-0.288, P<0.05), LVEF (r=0.377, P<0.05) and pro-BNP level (r=-0.294, P<0.05). Multivariable logistic regression analysis suggested that vasostatin-2, conventional risk factors, severity of HF stages and LVEF were independently associated with MACE in CHF patients. Vasostatin-2 (100μg) or PBS was injected intraperitoneally every other day in MI rats, follow by echocardiography, hemodynamic analysis after 2months. Compared with PBS, vasostatin-2 treatment prevented ischemic HF in MI rats, accompanied with reduction of infarct size, remodeling, fibrosis and inflammation, mainly through inhibition of Rho, Wnt and TLR-4 pathways and modulation of renin-angiotensin system.

Conclusion: Decreased serum vasostatin-2 level is associated with ischemic CHF and with MACE in three-year follow-up. Intraperitoneal injection of vasostatin-2 protects against ischemic HF in MI rats.

Keywords: Ischemic heart failure; MACE; Vasostatin-2.

MeSH terms

  • Aged
  • Animals
  • China / epidemiology
  • Chromogranin A* / analysis
  • Chromogranin A* / blood
  • Disease Models, Animal
  • Echocardiography / methods
  • Female
  • Fibrosis / metabolism
  • Fibrosis / prevention & control*
  • Follow-Up Studies
  • Heart Failure* / blood
  • Heart Failure* / diagnosis
  • Heart Failure* / etiology
  • Heart Failure* / physiopathology
  • Humans
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Male
  • Middle Aged
  • Myocardial Infarction* / complications
  • Myocardial Infarction* / epidemiology
  • Myocardial Infarction* / prevention & control
  • Myocardial Ischemia* / blood
  • Myocardial Ischemia* / prevention & control
  • Peptide Fragments* / analysis
  • Peptide Fragments* / blood
  • Protective Factors
  • Rats

Substances

  • Chromogranin A
  • Peptide Fragments
  • vasostatin II