Higher levels of TWEAK and matrix metalloproteinase-3 during the acute phase of myocardial infarction are associated with adverse left ventricular remodeling.

Abstract

IntroductionIt is known that the levels of tumor necrosis factor-like weak inducer of apoptosis (TWEAK/TNFSF12) increase after myocardial infarction (MI) and that it interacts with sCD163. It has also been argued that TWEAK can induce matrix metalloproteinases (MMPs) in macrophages.AimTo investigate the roles of TWEAK, sCD163, and MMPs in left ventricular (LV) adverse remodeling (AR) in the early post-MI period.Material and methodsForty-six patients with ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention were enrolled in the study. Post-MI LV functions and volumes were assessed by cardiac magnetic resonance imaging at 2 weeks and 6 months. Cytokines and MMPs were measured using a bead-based multiplex immunoassay system at 1 day (baseline) and 2 weeks post-MI. AR was defined as an increase in LV end-diastolic volume of ≥ 10% at the 6-month follow up.ResultsThe TWEAK, MMP-2, and MMP-3 baseline levels were higher in the patients with AR than those without AR. At 2 weeks post-MI, these expression levels were similar in patients with and without AR, but sCD163 expression was increased in patients without AR. The TWEAK and MMP levels were positively correlated in the early period post-MI. At first day post-MI, higher levels of TWEAK and MMP-3 were predictors of AR (OR = 1.03, p = 0.006; OR = 1.08, p = 0.015; respectively).ConclusionsTWEAK can induce MMPs in the early period post-MI, and these higher levels contribute to development of AR. Increased sCD163 levels at 2 weeks post-MI seem to be associated with the healing process through neutralizing the excessive inflammatory effects of TWEAK.