Dataset Information

Comprehensive Analysis and Co-Expression Network of mRNAs and lncRNAs in Pressure Overload-Induced Heart Failure.

ABSTRACT: Aim: Heart failure (HF) is the end stage of various cardiovascular diseases. However, the precise regulation of gene expression profiles and functional mechanisms of long non-coding RNAs (lncRNAs) in HF remain to be elucidated. The present study aimed to identify the differentially expressed profiles and interaction of messenger RNAs (mRNAs) and lncRNAs in pressure overload-induced HF. Methods: Male Sprague-Dawley rats were randomly divided into the HF group and the sham-operated group. HF was induced by the transverse aortic constriction (TAC) surgery. The cardiac expression profiles of mRNAs and lncRNAs in HF were investigated using the microarray. Bioinformatics analyses and co-expression network construction were performed from the RNA sequencing data. Results: The expression profiles of mRNAs and lncRNAs showed significant differences between HF and controls. A total of 147 mRNAs and 162 lncRNAs were identified to be differentially expressed with a fold change of >2 in HF. The relative expression levels of several selected mRNAs and lncRNAs were validated by quantitative PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that diverse pathways were involved in the molecular mechanisms of cardiac hypertrophy and HF including immune response, smooth muscle contraction, ion transmembrane transport. The mRNA-lncRNA and transcription factors (TFs)-lncRNA co-expression networks were constructed and several genes and TFs were identified as key regulators in the pathogenesis of HF. Further functional prediction showed that the lncRNA NONRATT013999 was predicted to cis-regulate mRNA CDH11, and NONRATT027756 was predicted to trans-regulate HCN4. Conclusion: This study revealed specific expression regulation and potential functions of mRNAs and lncRNAs in pressure overload-induced HF. These results will provide new insights into the underlying mechanisms and potential therapeutic targets for HF.

SUBMITTER: Chen S

PROVIDER: S-EPMC6920101 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Comprehensive Analysis and Co-Expression Network of mRNAs and lncRNAs in Pressure Overload-Induced Heart Failure.

Chen Shuping S Ma Qiong Q Xue Yanbo Y Zhang Jingwen J Yang Guodong G Wang Tingzhong T Ma Aiqun A Bai Ling L

Frontiers in genetics 20191212

<b>Aim:</b> Heart failure (HF) is the end stage of various cardiovascular diseases. However, the precise regulation of gene expression profiles and functional mechanisms of long non-coding RNAs (lncRNAs) in HF remain to be elucidated. The present study aimed to identify the differentially expressed profiles and interaction of messenger RNAs (mRNAs) and lncRNAs in pressure overload-induced HF. <b>Methods:</b> Male Sprague-Dawley rats were randomly divided into the HF group and the sham-operated g ...[more]

PMID: 31921308

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Project description:AimsLymphatics are essential for cardiac health, and insufficient lymphatic expansion (lymphangiogenesis) contributes to development of heart failure (HF) after myocardial infarction. However, the regulation and impact of lymphangiogenesis in non-ischaemic cardiomyopathy following pressure-overload remains to be determined. Here, we investigated cardiac lymphangiogenesis following transversal aortic constriction (TAC) in C57Bl/6 and Balb/c mice, and in end-stage HF patients.Methods and resultsCardiac function was evaluated by echocardiography, and cardiac hypertrophy, lymphatics, inflammation, oedema, and fibrosis by immunohistochemistry, flow cytometry, microgravimetry, and gene expression analysis. Treatment with neutralizing anti-VEGFR3 antibodies was applied to inhibit cardiac lymphangiogenesis in mice. We found that VEGFR3-signalling was essential to prevent cardiac lymphatic rarefaction after TAC in C57Bl/6 mice. While anti-VEGFR3-induced lymphatic rarefaction did not significantly aggravate myocardial oedema post-TAC, cardiac immune cell levels were increased, notably myeloid cells at 3 weeks and T lymphocytes at 8 weeks. Moreover, whereas inhibition of lymphangiogenesis did not aggravate interstitial fibrosis, it increased perivascular fibrosis and accelerated development of left ventricular (LV) dilation and dysfunction. In clinical HF samples, cardiac lymphatic density tended to increase, although lymphatic sizes decreased, notably in patients with dilated cardiomyopathy. Similarly, comparing C57Bl/6 and Balb/c mice, lymphatic remodelling post-TAC was linked to LV dilation rather than to hypertrophy. The striking lymphangiogenesis in Balb/c was associated with reduced cardiac levels of macrophages, B cells, and perivascular fibrosis at 8 weeks post-TAC, as compared with C57Bl/6 mice that displayed weak lymphangiogenesis. Surprisingly, however, it did not suffice to resolve myocardial oedema, nor prevent HF development.ConclusionsWe demonstrate for the first time that endogenous lymphangiogenesis limits TAC-induced cardiac inflammation and perivascular fibrosis, delaying HF development in C57Bl/6 but not in Balb/c mice. While the functional impact of lymphatic remodelling remains to be determined in HF patients, our findings suggest that under settings of pressure-overload poor cardiac lymphangiogenesis may accelerate HF development.

Dataset Information

Comprehensive Analysis and Co-Expression Network of mRNAs and lncRNAs in Pressure Overload-Induced Heart Failure.

Publications

Comprehensive Analysis and Co-Expression Network of mRNAs and lncRNAs in Pressure Overload-Induced Heart Failure.

Similar Datasets

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