Potential implication of microRNA21 and matrix metalloproteinases in myocardial and arterial function in patients with coronary disease and type-2 diabetes at baseline and 1-year follow up

Abstract Background Circulating microRNAs, particularly miR21, are known to be involved in cardiovascular diseases and atherosclerotic processes. However, their role in the setting of ST-elevation myocardial infarction (STEMI), and their predictive role of left ventricular (LV) dysfunction is less clear. Aim To determine the association of circulating miR21, as well as MMP1 and MMP 9, with LV ejection fraction (LVEF), global longitudinal strain (GLS), and arterial function, in patients with STEMI and chronic coronary syndromes (CCS), at baseline and 1-year follow-up. Methods 90 patients (61% men, 58+/-12 years), including 60 patients with STEMI (30 patients with type 2 diabetes (T2D), 30 patients without T2D), and 30 patients with CCS were assessed within 24 hours of admission by serum microRNA quantification, and serum MMP-1 and MMP-9 analysis. At baseline and 1-year follow up, 2D and 3D echocardiography were used to assess LVEF; speckle tracking to asses GLS, radial strain (RS), circumferential strain (CS), and area strain (AS); CAVI and ABI to assess arterial function. Results miR21 and MMP1 were significantly higher in patients with STEMI vs. CCS. In patients with STEMI, at 1-year there was a significant increase of 2D and 3D LVEF (p0.04), 2D and 3D GLS (p0.001), and 3D RS and AS (p=0.03). By univariate analysis, MMP1 correlated with changes of R-CAVI and L-CAVI (r=0.36 and r=0.32, both p0.01), while miR21 correlated with changes of 3D LVEF (r=-0.32, p0.05), CS (r=-0.36, p=0.02), and RS (r=-0.38, p=0.01). In patients with STEMI without diabetes, miR21 correlated with 3D GLS, CS, RS, and AS (r of -0.52, -0.53, -0.53, -0.60, all p=0.01). In patients with CCS, MMP9 correlated with RABI and LABI (r of -0.48, -0.43, all p0.05), while miR21 correlated with 2D and 3D GLS (r of 0.89, 0.83, all p0.05). Reduction of miR21 was an independent predictor of increase of 3D GLS in patients with STEMI without T2D (r²=0.27, p=0.01), while increase of miR21 was an independent predictor of increase of 2DGLS in patients with CCS (r²=0.79, p=0.01) at one-year. Conclusions Circulating miR21, as well as MMP1 and MMP9, are potential biomarkers of ventricular function in patients with STEMI, correlating with myocardial deformation parameters and showing potential predictive roles. However, further studies are needed to establish their role in cardiovascular diseases.