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

• Published in: International journal of cardiology 2016-10, Vol.221, p.1-11
• Main Authors: Pan, Wen Qi, He, Yu Hu, Su, Qian, Yang, Jie, Fang, Yue Hua, Ding, Feng Hua, Yan, Xiao Xiang, Liu, Zhu Hui, Wang, Xiao Qun, Yang, Ke, Zhang, Rui Yan, Shen, Wei Feng, Zhang, Feng Ru, Lu, Lin
• Format: Article
• Language: English
• Subjects: Aged; Animals; Cardiovascular; 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; Ischemic heart failure; MACE; 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; Vasostatin-2
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2016.06.065

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 (100 μg) or PBS was injected intraperitoneally every other day in MI rats, follow by echocardiography, hemodynamic analysis after 2 months. 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.