Transcriptional profiling of left ventricle and peripheral blood mononuclear cells in a rat model of postinfarction heart failure

Abstract

BackgroundMyocardial infarction (MI) often results in left ventricular (LV) remodeling followed by heart failure (HF). It is of great clinical importance to understand the molecular mechanisms that trigger transition from compensated LV injury to HF and to identify relevant diagnostic biomarkers. The aim of this study was to investigate gene expression in the LV and to evaluate their reflection in peripheral blood mononuclear cells (PBMCs).MethodsMI was induced in rats by ligation of the proximal left coronary artery. Rats with small, moderate, and large MI size were included into the experiment two months after the operation. The development of heart failure was estimated by echocardiography and catheterization. Microarrays were used to compare the LV and PBMCs transcriptomes of control and experimental animals.ResultsOnly rats with a large MI developed extensive LV remodeling and heart failure. 840 transcripts were altered in LV of failing hearts, and especially numerous were those associated with the extracellular matrix. In contrast, no significant gene expression changes were seen in LVs of rats with moderate or small MI that had compensated LV injury. We showed that ceruloplasmin was similarly overexpressed in the heart and blood in response to HF, whereas downregulation of tetraspanin 12 was significant only in the PBMCs.ConclusionA large size of infarcted area is critical for progression of LV remodeling and HF development, associated with altered gene expression in the heart. Ceruloplasmin and tetraspanin 12 are potential convenient markers in readily obtainable PBMCs.

New genetic variants associated with major adverse cardiovascular events in patients with acute coronary syndromes and treated with clopidogrel and aspirin

“…We mined four publicly available genome-wide expression data sets from Gene Expression Omnibus (GEO) database in NCBI, including GSE27962 [ 23 ], GSE48060 [ 24 ], GSE7487 [ 25 ] and GSE47495 [ 26 ]. These datasets recorded gene expression data of cardiac remodeling after myocardial infarction or myocardial infarction-induced heart failure.…”

New genetic variants associated with major adverse cardiovascular events in patients with acute coronary syndromes and treated with clopidogrel and aspirin

“…We mined four publically available genome-wide expression data sets from Gene Expression Omnibus (GEO) database in NCBI, including GSE27962 [12], GSE48060 [13], GSE7487 [14] and GSE47495 [15]. These datasets recorded gene expression data of cardiac remodeling after myocardial infarction or Myocardial Infarction-Induced Heart Failure.…”

“…To further explore the functional evidence of the six genetic predispositions that contribute to MACE, we searched all literatures referring to the six genes and cardiovascular diseases in PubMed database. Meanwhile, we also mined several publicly available genome-wide expression data sets from the GEO database, [12][13][14][15] which recorded cardiac remodeling data after myocardial infarction (MI). We found two of six genes, MYOM2 and ECHS1, showed abundant evidences of decreased expression in cases with adverse cardiac events, either in previous reports or in our data analysis.…”

“…M-Protein (myomesin-2) encoded by MYOM2 or total myomesin is down-regulated either in cardiac hypertrophy in rats, [18] in acute myocardial infarction (AMI) patients, [19] or in chronic heart failure. [20] Similarly, ECHS1, as an ischaemic post-conditioning (PostC) modified protein, showed significantly decreased expression in the cardiac remodeling group after MI compared with the sham group, by analyzing the two different groups' expression data from GEO database GSE7487 [14] (12,930 ± 337 vs. 16,360 ± 466, P = 5.46 × 10 −6 ) and GSE47495 [15] (11.89 ± 0.11 vs. 12.13 ± 0.04 , P = 7.28 × 10 −4 , Table S7). Meanwhile, we compared the plasma ECHS1 protein levels in ACS patients with HF symptoms at New York Heart Association (NYHA) stage III or IV (n=89) to those with HF symptoms at NYHA stage II or less (n=61).…”

AAV9-TAZ Gene Replacement Ameliorates Cardiac TMT Proteomic Profiles in a Mouse Model of Barth Syndrome

“…BTHS standard of care currently includes administration of medications, such as diuretics and angiotensin-converting enzyme (ACE) inhibitors—there is currently no disease-modifying therapy for this disorder 12 . In addition, previous studies have indicated that cardiac TAZ mRNA expression is diminished in several heart failure animal models, chronic human heart failure patients, and human patients with dilated cardiomyopathy, suggesting that tafazzin expression influences both BTHS and common heart failure 3, 14, 15, 16, 17, 18…”