The Long Noncoding RNA Landscape of the Ischemic Human Left Ventricle

Abstract

Background The discovery of functional classes of long noncoding RNAs (lncRNAs) has expanded our understanding of the variety of RNA species that exist in cells. In the heart, lncRNAs have been implicated in the regulation of development, ischemic and dilated cardiomyopathy, and myocardial infarction. Nevertheless, there is a limited description of expression profiles for these transcripts in human subjects. Methods and Results We obtained left ventricular tissue from human patients undergoing cardiac surgery and used RNA sequencing to describe a lncRNA profile. We then identified a list of lncRNAs that were differentially expressed between pairs of samples before and after the ischemic insult of cardiopulmonary bypass. The expression of some of these lncRNAs correlates with ischemic time. Coding genes in close proximity to differentially expressed lncRNAs as well as coding genes that have coordinated expression with these lncRNAs are enriched in functional categories related to myocardial infarction including: heart function, metabolism, the stress response, and the immune system. Conclusions We describe a list of lncRNAs that are differentially expressed after ischemia in the human heart. These genes are predicted to function in pathways consistent with myocardial injury. As a result, lncRNAs may serve as novel diagnostic and therapeutic targets for ischemic heart disease. Clinical Trial Registration https://clinicaltrials.gov/; Unique Identifier: NCT00985049.

Long non‑coding RNA GAS5 regulates myocardial ischemia‑reperfusion injury through the PI3K/AKT apoptosis pathway by sponging miR‑532‑5p

“…lncRNA has been revealed to be involved in the pathophysiological processes of various tumor types, including in cell growth, proliferation, invasion and apoptosis (14,15). A number of studies have considered the effects of lncRNAs that serve functions in myocardial ischemia (16,17). A number of lncRNAs have been reported to be involved in the regulation of myocardial ischemia by exerting their biological mechanisms (18,19).…”

Expedition to the missing link: Long noncoding RNAs in cardiovascular diseases

“…The roles of lncRNAs in heart failure (HF) have been investigated extensively using high-throughput RNA sequencing both in human [24][25][26] and animal models [27][28][29][30]. Using deep RNA sequencing on myocardial RNA samples from human HF patients before and after left ventricular assisted device (LVAD) support, we have revealed the dynamic regulation of myocardial transcriptome, including mRNA, miRNA and lncRNA, in advanced HF and after LVAD support.…”

Long non-coding RNAs in the failing heart and vasculature

“…Several other lncRNAs have been implicated in MI, including myocardial infarction-associated transcript 2 ( MIRT2 ) [ 120 ], NONRATT021972 [ 121 , 122 ], and MHRT [ 123 ]. In addition, transcriptome analysis of heart tissue identified novel lncRNAs that are possibly involved in processes underlying cardiac ischaemic injury in mouse and human [ 124 , 125 ]. However, the precise role of these lncRNAs in cardiac fibrosis and ischaemic heart disease remains elusive.…”