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

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiaoling Zhang ◽  
◽  
Jeroen G. J. van Rooij ◽  
Yoshiyuki Wakabayashi ◽  
Shih-Jen Hwang ◽  
...  

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.

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Tianqi Xia ◽  
Bikash Ranjan Giri ◽  
Jingyi Liu ◽  
Pengfei Du ◽  
Xue Li ◽  
...  

Abstract Background Schistosomiasis is a chronic, debilitating infectious disease caused by members of the genus Schistosoma. Previous findings have suggested a relationship between infection with Schistosoma spp. and alterations in the liver and spleen of infected animals. Recent reports have shown the regulatory role of noncoding RNAs, such as long noncoding RNAs (lncRNAs), in different biological processes. However, little is known about the role of lncRNAs in the mouse liver and spleen during Schistosoma japonicum infection. Methods In this study, we identified and investigated lncRNAs using standard RNA sequencing (RNA-Seq). The biological functions of the altered expression of lncRNAs and their target genes were predicted using bioinformatics. Ten dysregulated lncRNAs were selected randomly and validated in reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) experiments. Results Our study identified 29,845 and 33,788 lncRNAs from the liver and spleen, respectively, of which 212 were novel lncRNAs. We observed that 759 and 789 of the lncRNAs were differentially expressed in the respective organs. The RT-qPCR results correlated well with the sequencing data. In the liver, 657 differentially expressed lncRNAs were predicted to target 2548 protein-coding genes, whereas in the spleen 660 differentially expressed lncRNAs were predicted to target 2673 protein-coding genes. Moreover, functional annotation showed that the target genes of the differentially expressed lncRNAs were associated with cellular processes, metabolic processes, and binding, and were significantly enriched in metabolic pathways, the cell cycle, ubiquitin-mediated proteolysis, and pathways in cancer. Conclusions Our study showed that numerous lncRNAs were differentially expressed in S. japonicum-infected liver and spleen compared to control liver and spleen; this suggested that lncRNAs may be involved in pathogenesis in the liver and spleen during S. japonicum infection.


2021 ◽  
Vol 22 (Supplement_3) ◽  
Author(s):  
G Koulaouzidis

Abstract Funding Acknowledgements Type of funding sources: None. Background Coronary atherosclerosis is a continuous process beginning early in life, with a long and clinically asymptomatic phase, before manifestations appear in middle and/or late adulthood. Coronary artery calcification (CAC) is a well-established marker of atherosclerosis; but the clinical validity of CAC in young adults (traditionally considered as a population group of low cardiovascular risk) remains unclear. Aim We aimed to assess the prevalence of CAC in a population of young individuals without previous history of coronary artery disease (CAD) in the UK and its association with conventional cardiovascular risk factors. Methods This analysis includes 4186 asymptomatic young individuals who underwent electron beam computed tomography (EBCT). Demographic information and the presence of cardiovascular risk factors were abstracted from referral letters and/or questionnaires completed by the patients prior to their tests. Individuals with previously documented CAD or chronic kidney disease were excluded. All EBCT CAC studies were performed using the same scanner (Imatron C300 Ultrafast computed tomography scanner, GE Healthcare, London, UK) and the same scanning protocol. Results The age (mean SD) of the study cohort was 40.5 ±3.6 years (range 26–45 years, 83.8% males). Hypertension, dyslipidemia, and diabetes mellitus (DM) were present in 15.5, 7.9, and 2.8% of individuals, respectively. Family history of premature CAD was present in 17% and 17.4% were smokers.  CAC was present in 21.8% of the cohort, while individuals with CAC comparing with those with CAC score 0 were males (95.2 vs. 80%, p &lt; 0.002), older in age (41.4 3.2 vs. 40.3 3.7 years, p &lt; 0.0001), with DM (5.5 vs. 25%, p &lt; 0.0001), hypertension (22 vs. 13.7%, p &lt; 0.0001), and dyslipidemia (14.8 vs. 6%, p &lt; 0.0001). The prevalence of CAC score 0, 1–100, 101–400, 401–1000, &gt;1000 were 78.2, 19, 2.1, 0.5, and 0.2%, respectively. The prevalence and distribution of CAC among various age groups are shown in Table 1. CAC was found in 24.8% of males (CAC score 1–100, 101–400, 400–1000, &gt;1000 in 21.6, 2.5, 0.5, and 0.1%, respectively) and 6.6% of females (CAC score 1–100, 101–400, 400–1000, &gt;1000 in 5.4, 0.6, 0.15 and 0.4%, respectively) (p &lt; 0.0001). There was no statistical difference of mean CAC score between genders (males 13.8 72.7; females 11.8 142.4; p = 0.6). In multivariate analysis, the presence of CAC was associated with age (p&lt; 0.0001), male gender (p&lt; 0.0001), DM (p&lt; 0.0001), hypertension (p&lt; 0.0001), and dyslipidemia (p&lt; 0.0001).  Conclusion   In a large cohort of asymptomatic young individuals, subclinical atherosclerosis (CAC score &gt;0) was identified in approximately 20%. Assessment of CAC score is a useful clinical tool in young individuals, as it can confirm the presence of subclinical atherosclerosis.


2014 ◽  
Vol 7 (7) ◽  
pp. 679-686 ◽  
Author(s):  
Andre R.M. Paixao ◽  
Jarett D. Berry ◽  
Ian J. Neeland ◽  
Colby R. Ayers ◽  
Anand Rohatgi ◽  
...  

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
N Pogosova ◽  
NP Kachanova ◽  
YM Yufereva ◽  
OY Sokolova ◽  
IE Koltunov ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background Coronary atherosclerosis has a long subclinical period. It’s early detection may offer a possibility of timely initiation of preventive interventions Purpose To develop a diagnostic rule for detection of patients (pts) with high probability of subclinical atherosclerosis among those with high or very high cardiovascular (CV) risk. Methods This cross-sectional study enrolled 52 pts (32 men [62%]), aged 40 to 65 years [mean age 54.6 ± 8.0]) with high or very high CV risk (5-9 and ≥10% by The Systematic Coronary Risk Estimation Scale [SCORE], respectively). All participants underwent cardiac computed tomography (CT) angiography and calcium scoring. Traditional risk factors (RFs) (family history of premature CVD, smoking, overweight/obesity and abdominal obesity, hypertension, type 2 diabetes mellitus, lipids parameters (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides) and lipids-related markers (apolipoprotein A1, apolipoprotein B, ApoB/ApoA1 ratio), biomarkers of inflammation (high-sensitivity C-reactive protein [hs CRP], fibrinogen), indicator carbohydrate metabolism (glucose),  ankle-brachial index,  stress-test, carotid plaques according to ultrasound were evaluated in all pts. Psychological RFs were evaluated using Hospital Anxiety and Depression Scale and DS-14 for type D personality. Results All pts were divided into 2 groups according to the CT angiography results: pts in the main group (n = 21) had any non-obstructive lesions or calcium score &gt;0, pts in the control group (n = 31) had intact coronary arteries. The groups did not differ in age or gender. 26 multiple linear logistic models for any subclinical atherosclerosis were developed based on obtained diagnostic features. Taking into account R-square = 0.344 (p = 0.0008), the best fitting model was follows:  subclinical coronary atherosclerosis= -1.576 + 0.234 x SCORE ≥5%  + 0.541 x hs CRP &gt;2 g/l + 0.015 x heart rate  (bpm) + 0.311 family history of premature CVD.  The developed algorithm had sensitivity of 63% and  specificity of 80%. Conclusions The created diagnostic model diagnostic model suggests the presence of subclinical coronary atherosclerosis in patients with high / very high CV risk with a high degree of probability. This easy-to-use method can be used in routine clinical practice to improve risk stratification and management choices in high-risk pts.


2011 ◽  
Vol 73 (4) ◽  
pp. 350-357 ◽  
Author(s):  
Timothy W. Smith ◽  
Bert N. Uchino ◽  
Paul Florsheim ◽  
Cynthia A. Berg ◽  
Jonathan Butner ◽  
...  

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