Clinical significance of increased urotensin II levels in acute myocardial infarction.

We aimed to study urotensin II (UII) in acute myocardial infarction (AMI) patients before and after percutaneous coronary intervention (PCI) and to investigate its interaction with angiotensin II (ATII) in post-AMI myocardial remodeling. In this clinical study, 63 AMI patients and 66 controls were included. Levels of UII, ATII, and NT-B-type natriuretic peptide (NT-BNP) were determined. Participants were followed up for 2 years to observe clinical outcomes. In cell biology experiments, ATII and UII were added into cardiomyocytes and fibroblasts individually or in combination. Effects of ATII and UII on cardiac hypertrophy and fibrosis were observed. UII levels increased significantly after AMI (P < 0.001), especially after PCI (P = 0.0009), and was an independent predictor of death (OR 0.007, P = 0.005). UII correlated negatively with hypertension risk stratifications (P = 0.047) and the number of coronary artery lesions (P = 0.029), whereas it correlated positively with left ventricular ejection fraction (P = 0.0395). Myocardial ERK phosphorylations (P = 0.0041) were promoted and the expressions of cardiac hypertrophy-related genes (BNP, ANP) were upregulated in cells treated with ATII and UII (P < 0.005). The ATII+UII group also had significant increases of matrix metalloproteinase-2 (MMP-2), metalloproteinase-9 (MMP9), and fibronectin expressions, as well as collagen type I, III, MMP2, and MMP9 gene transcriptions (all P < 0.05). The UII level rose in AMI and was a predictor of death, but at the right concentration it may also have a cardioprotective role. Our findings suggest that UII and ATII have synergistic effects on cardiomyocyte remodeling. UII may play a role in the myocardial healing process post-AMI.