Preclinical Development of a MicroRNA-Based Therapy for Elderly Patients With Myocardial Infarction

Abstract

We concluded that miR-22 is an important regulator of cardiac autophagy and a potential therapeutic target, especially in the older myocardium. Finally, circulating miR-22 provides prognostic information for HF patients, highlighting miR-22 as a promising therapeutic and biomarker candidate for cardiovascular disorders.

How to be young at heart? miR-22 as a potential therapeutic target to boost autophagy and protect the old myocardium

“…The increase in cardiac miR-22 levels during aging was paralleled by a progressive decline in myocardial autophagy. Importantly, miR-22 inhibition appears to rescue autophagy in aging hearts (11). miR-22 may have autophagy-independent actions, and thus, the causative involvement of autophagy in mediating the salutary actions of miR-22 inhibition remains to be demonstrated.…”

“…Using high-throughput screening based on the fluorescence-activated cell sorting-based detection of GFP-LC3 protein and library screening, Gupta et al identified miR-22 as a strong inhibitor of autophagy in cardiomyocytes (11). The authors showed that miR-22 inhibits the reduction in GFP-LC3 signal in response to starvation, an established stimulus for autophagy.…”

“…Gupta et al demonstrated that miR-22 expression progressively increases in the mouse heart during aging (11). miR-22 inhibition by locked nucleic acid-based antimiR-22 (LNA-anti-miR-22) significantly attenuated cardiac remodeling in old mice subjected to permanent coronary artery ligation, reducing left ventricular dilation and improving systolic function.…”

Interactions between microRNAs and long non-coding RNAs in cardiac development and repair

“…Gupta et al employed an aged mice model to study the effect of anti-miR22 therapy following AMI and, compared to younger mice, old mice were shown to have higher expression levels of miR-22, a key regulator for cardiac autophagy [65]. for the cardiac hypertrophy in HF murine models [69].…”

Which future for circulating microRNAs as biomarkers of acute myocardial infarction?

“…A 4-miRNA panel including miR-150 improved outcome prediction in a cohort of 150 AMI patients (9). In a recent case/control study with 198 patients, circulating levels of miR-22 were independent predictors of cardiovascular mortality in patients with systolic heart failure from both ischemic and nonischemic origin (10).…”