Abstract
Myocardial infarction (MI) is one of the most frequent cardiac emergencies, with significant potential for mortality. One of the major challenges of the post-MI healing response is that replacement fibrosis could lead to left ventricular remodeling (LVR) and heart failure (HF). This process involves canonical and non-canonical transforming growth factor-beta (TGF-β) signaling pathways translating into an intricate activation of cardiac fibroblasts and disproportionate collagen synthesis. Accumulating evidence has indicated that microRNAs (miRNAs) significantly contribute to the modulation of these signaling pathways. This review summarizes the recent updates regarding the molecular mechanisms underlying the role of the over 30 miRNAs involved in post-MI LVR. In addition, we compare the contradictory roles of several multifunctional miRNAs and highlight their potential use in pressure overload and ischemia-induced fibrosis. Finally, we discuss their attractive role as prognostic biomarkers for HF, highlighting the most relevant human trials involving these miRNAs.
Highlights
Coronary artery disease (CAD) is the leading cause of death for both women and men in developed as well as in developing countries, acute myocardial infarction (MI) being responsible for most of the CAD mortality [1]
Only day 5 miR-29a levels showed a positive association with day 90 LVEDV. These findings suggest that miR-1 has no prognostic value for post-MI left ventricular remodeling (LVR) and that early miR-29a increase in the blood correlates with a negative outcome of post-MI LVR
The results showed that both miR-21 or miR-146a could be used as early biomarkers of LVR, and their combination might have a higher predictive power
Summary
Coronary artery disease (CAD) is the leading cause of death for both women and men in developed as well as in developing countries, acute myocardial infarction (MI) being responsible for most of the CAD mortality [1]. Cardiac remodeling involves three intricate and complex processes (apoptosis, hypertrophy, and fibrosis), of which fibrosis is the main component of post-MI LVR. Besides the Smad canonical pathway, TGF-β activates many non-canonical signaling pathways, such as ERK (extracellular signal-regulated kinase), MAPK (mitogen-activated protein kinase), AKT (protein kinase B), and NF-κB (nuclear factor kappa-light-chainenhancer of activated B cells) pathways. This leads to proliferation, differentiation, and the activation of fibroblasts, which deposit ECM components in the surrounding tissue [11,12]. MiR-125b miR-133a miR-144 inhibitor 1; c-Myb, member of proto-oncogene family Myb; COL1A1, collagen type 1, alpha 1 gene; COL1A2, collagen type 1, alpha 2 gene; CTGF, connective tissue growth factor; ELN, elastin gene; ENG, endoglin; FBN, fibrillin gene; RI, transforming growth factor-beta receptor I; RII, transforming growth factor-beta receptor II; Smad 2, 3, 4, 7, 2/3, SMAD family members; Snai, snail family zinc finger 1; Sp1, specificity protein 1; TGF-β, transforming growth factor-beta
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