Cardiac Metabolism and MiRNA Interference

Abstract

The aberrant increase in cardio-metabolic diseases over the past couple of decades has drawn researchers’ attention to explore and unveil the novel mechanisms implicated in cardiometabolic diseases. Recent evidence disclosed that the derangement of cardiac energy substrate metabolism plays a predominant role in the development and progression of chronic cardiometabolic diseases. Hence, in-depth comprehension of the novel molecular mechanisms behind impaired cardiac metabolism-mediated diseases is crucial to expand treatment strategies. The complex and dynamic pathways of cardiac metabolism are systematically controlled by the novel executor, microRNAs (miRNAs). miRNAs regulate target gene expression by either mRNA degradation or translational repression through base pairing between miRNA and the target transcript, precisely at the 3’ seed sequence and conserved heptametrical sequence in the 5’ end, respectively. Multiple miRNAs are involved throughout every cardiac energy substrate metabolism and play a differential role based on the variety of target transcripts. Novel theoretical strategies have even entered the clinical phase for treating cardiometabolic diseases, but experimental evidence remains inadequate. In this review, we identify the potent miRNAs, their direct target transcripts, and discuss the remodeling of cardiac metabolism to cast light on further clinical studies and further the expansion of novel therapeutic strategies. This review is categorized into four sections which encompass (i) a review of the fundamental mechanism of cardiac metabolism, (ii) a divulgence of the regulatory role of specific miRNAs on cardiac metabolic pathways, (iii) an understanding of the association between miRNA and impaired cardiac metabolism, and (iv) summary of available miRNA targeting therapeutic approaches.

Molecular mechanisms of metabolic dysregulation in diabetic cardiomyopathy

“…The pathological mechanism of diabetic cardiomyopathy is also related to the expression of non-coding RNA. MiRNA binds to the 3′ untranslated region (UTR) of messenger RNA (mRNA) molecule and regulates the expression of cardiac metabolism-related genes at the post-transcriptional level through mRNA translation inhibition or degradation ( 121 ). MiR-320 is highly expressed in diabetic cardiomyopathy mice and diabetic patients ( 18 ).…”

New Insight into Mechanisms of Cardiovascular Diseases: An Integrative Analysis Approach to Identify TheranoMiRNAs

“…MiRNAs regulate both physiological and pathological heart functions, playing important epigenetic roles in gene regulation and cell function [ 1 , 2 ]. Altered expression of miRNAs is associated with heart metabolism dysregulation, heart injury, heart fibrosis, and, in general, cardiovascular diseases (CVDs), making miRNAs attractive therapeutic strategies for the diagnosis and treatment of heart diseases [ 3 , 4 ].…”