Genome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification

Abstract

Background Coronary artery calcification (CAC) is a noninvasive measure of coronary atherosclerosis, the proximal pathophysiology underlying most cases of myocardial infarction (MI). We sought to identify expression signatures of early MI and subclinical atherosclerosis in the Framingham Heart Study (FHS). In this study, we conducted paired-end RNA sequencing on whole blood collected from 198 FHS participants (55 with a history of early MI, 72 with high CAC without prior MI, and 71 controls free of elevated CAC levels or history of MI). We applied DESeq2 to identify coding-genes and long intergenic noncoding RNAs (lincRNAs) differentially expressed in MI and high CAC, respectively, compared with the control. Results On average, 150 million paired-end reads were obtained for each sample. At the false discovery rate (FDR) < 0.1, we found 68 coding genes and 2 lincRNAs that were differentially expressed in early MI versus controls. Among them, 60 coding genes were detectable and thus tested in an independent RNA-Seq data of 807 individuals from the Rotterdam Study, and 8 genes were supported by p value and direction of the effect. Immune response, lipid metabolic process, and interferon regulatory factor were enriched in these 68 genes. By contrast, only 3 coding genes and 1 lincRNA were differentially expressed in high CAC versus controls. APOD, encoding a component of high-density lipoprotein, was significantly downregulated in both early MI (FDR = 0.007) and high CAC (FDR = 0.01) compared with controls. Conclusions We identified transcriptomic signatures of early MI that include differentially expressed protein-coding genes and lincRNAs, suggesting important roles for protein-coding genes and lincRNAs in the pathogenesis of MI.

Whole-Blood Transcriptional Profiles Enable Early Prediction of the Presence of Coronary Atherosclerosis and High-Risk Plaque Features at Coronary CT Angiography

“…However, profiling was performed using microarrays, which are limited in dynamic range. Only recently have a few studies used RNA-Seq to look for transcriptional markers of the degree of coronary stenosis or related conditions, although in all of these the vessels were being investigated using invasive angiography in symptomatic patients [ 12 , 13 , 14 , 15 ].…”

“…Preliminary studies have identified gene expression profiles that would distinguish women with acute myocardial infarction (MI) with nonobstructive CAD from those with MI-CAD or controls [ 12 ], and subjects with coronary stenosis ≥50% from those with stenosis <50% [ 13 ]. Two larger studies documented transcriptional expression signatures that discriminated a low degree of stenosis (≤20%) from an intermediate degree (>20% but <70% in any vessel) in patients presenting for elective coronary catheterization [ 14 ], and subjects with early MI from those with subclinical coronary atherosclerosis (detected as a high degree of coronary artery calcification (CAC)) and from controls without a history of MI or high CAC [ 15 ]. In all these studies, the presence or absence of coronary atherosclerosis had been documented by invasive coronary angiography.…”

LINC00452 overexpression reverses oxLDL-induced injury of human umbilical vein endothelial cells (HUVECs) via regulating miR-194-5p/IGF1R axis

“…In addition, lncRNA NEXN-AS1 overexpression notably suppressed the development of AS via targeting Nexilin F-actin binding protein (19). Another study revealed that lncRNA LINC00452 was significantly downregulated in the whole blood of patients with CAD compared with healthy controls (14). In addition, the level of LINC00452 was much lower in patients with myocardial infarction, compared with that in patients with CAD (14).…”

“…Long non-coding RNAs (lncRNA), a type of non-coding RNAs (ncRNAs), with a transcript length of exceed 200 nt, which play significant roles in the progression of AS (13,14). In addition, microRNAs (miRNAs), another type of ncRNAs, can directly regulate the expression of messenger RNA (mRNA) via affecting their stability (15).…”

“…Another study revealed that lncRNA LINC00452 was significantly downregulated in the whole blood of patients with CAD compared with healthy controls (14). In addition, the level of LINC00452 was much lower in patients with myocardial infarction, compared with that in patients with CAD (14). Moreover, the progression of CAD could contribute to the occurrence of myocardial infarction (20).…”