Noncoding RNAs implication in cardiovascular diseases in the COVID-19 era

Abstract

COronaVIrus Disease 19 (COVID-19) is caused by the infection of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). Although the main clinical manifestations of COVID-19 are respiratory, many patients also display acute myocardial injury and chronic damage to the cardiovascular system. Understanding both direct and indirect damage caused to the heart and the vascular system by SARS-CoV-2 infection is necessary to identify optimal clinical care strategies. The homeostasis of the cardiovascular system requires a tight regulation of the gene expression, which is controlled by multiple types of RNA molecules, including RNA encoding proteins (messenger RNAs) (mRNAs) and those lacking protein-coding potential, the noncoding-RNAs. In the last few years, dysregulation of noncoding-RNAs has emerged as a crucial component in the pathophysiology of virtually all cardiovascular diseases. Here we will discuss the potential role of noncoding RNAs in COVID-19 disease mechanisms and their possible use as biomarkers of clinical use.

Keywords: COVID-19,; Cardiovascular disease; Noncoding RNAs,; SARS-CoV-2,; Transcriptomics.

Fig. 1

Differences between genome of SARS-CoV and SARS-CoV-2. The six regions of difference (RD) are indicated by red rectangles

Fig. 2

Time course of host responses to SARS-CoV infection in humans. A biphasic expression of inflammatory mediators is associated with the early disease, where the cellular infiltration into the lungs, peaks with the higher viral titer and the late disease that corresponds to viral clearance in non-complicated ARDS. The switch from innate to adaptive immune response is important for fighting ARDS

Fig. 3

The renin-angiotensin system. ACE2 can cleave both Angiotensin I and Angiotensin II to generate Ang 1-9 and Ang 1-7, respectively. Ang 1-9 and Ang 1-7, in turn, bind Angiotensin II Type 2 Receptor (AT2R) and MAS and have vasodilatory, pro-apoptotic, anti-fibrotic and anti-inflammatory effects. ACE2 converts Angiotensin I to Angiotensin II, which through the binding to AT1R has opposite effects, i.e. vasoconstriction, anti-apoptotic, pro-fibrotic and pro-inflammatory effects

Fig. 4

Noncoding RNAs dysregulation studied by genome-wide transcriptomic analysis. a Analysis of the molecular modifications underlying both cardiac hypertropy (HCM) and remodeling (DCM and ICM) allowed the identification of dysregulated miRNAs, lncRNAs and circRNAs in the heart. b The release of ncRNAs by diseased cardiac tissues in the peripheral blood and the immunomodulation associated to CVD allowed the identification of dysregulated ncRNAs in whole blood, plasma/serum or in PBMCs, to be used as potential biomarkers

Fig. 5

High-throughput analysis of transcriptomic changes induced by viral infection. Transcriptomic changes analyzed by single-cell RNA-seq analysis and bulk RNA-Seq. in a PBMCs from COVID-19 patients; b iPSC-derived cardiomyocytes infected in vitro by SARS-CoV2 virus. c Transcriptomic analysis of endomyocardial biopsies and plasma of viral-cardiomyopathy patients identified miRNAs with an established role also in CVDs. The main miRNAs and lncRNAs identified are shown. d Transcriptomic changes in the lungs of SARS-CoV infected mice or in lung biopsies from COVID-19 patients. Specific miRNAs and lncRNAs were shown to be differential expressed