Downregulation of microRNA-21-5p from macrophages-derived exosomes represses ventricular remodeling after myocardial infarction via inhibiting tissue inhibitors of metalloproteinase 3

Objective: Exosomes are known to transfer microRNAs (miRNAs) to affect the progression of human diseases. We aim to explore the role of M1 macrophages-derived exosomes (M1 exosomes) conveying miR-21-5p in ventricular remodeling in mice with myocardial infarction (MI) by regulating tissue inhibitors of metalloproteinase 3 (TIMP3). Methods: Macrophages were isolated and co-cultured with miR-21-5p antagomir to extract the exosomes. The modeled mice were injected with relative exosomes to investigate their roles in the cardiac function, pathology of myocardial tissue, myocardial fibrosis, cardiomyocyte apoptosis and ventricular remodeling in MI mice. The expression of miR-21-5p and TIMP3 was detected and their targeting relationship was analyzed. Results: MiR-21-5p was upregulated while TIMP3 was downregulated in MI mouse myocardial tissues. M1 exosomes impaired cardiac function, aggravated pathology of myocardial tissue, myocardial fibrosis and ventricular remodeling, and promoted cardiomyocyte apoptosis in MI mice. M1 exosomes containing miR-21-5p antagomir alleviated the above alterations, while the role of exosomes containing miR-21-5p antagomir was reversed by silencing TIMP3. TIMP3 was targeted by miR-21-5p. Conclusion: Downregulation of miR-21-5p from macrophages-derived exosomes suppresses ventricular remodeling after MI via inhibiting TIMP3.