GSE145697 The role of lncRNA Sarrah in human cardiomyocytes

Contributors : Reinier A Boon ; D J TrembinskiSeries Type : Expression profiling by arrayOrganism : Homo sapiensLong non-coding RNAs (lncRNAs) contribute to (patho)physiological processes in the heart. Aging is the major risk factor for cardiovascular disease and cardiomyocyte apoptosis is an underlying cause for age-related cardiac dysfunction. RNA sequencing of cardiomyocytes from young and aged mouse hearts revealed several aging-regulated lncRNAs. An siRNA screen for caspase activity identified the aging-regulated lncRNA Sarrah (ENSMUST00000140003) as anti-apoptotic, which we confirmed in human cells (human SARRAH is annotated as OXCT1-AS1). Importantly, human engineered heart tissue showed impaired contractile force development upon SARRAH knockdown compared with controls. Computational prediction of RNA-DNA triple helix formation showed that SARRAH may directly bind the promoters of genes downregulated after SARRAH silencing, which mainly consist of cell survival genes. Indeed, nuclear magnetic resonance spectroscopy confirmed RNA-DNA triple helix formation and cardiomyocytes lacking the triple helix-forming domain of Sarrah showed an increase in apoptosis. One of the key direct SARRAH targets is NRF2, an anti-oxidant transcription factor. Restoration of NRF2 levels after SARRAH silencing partially rescues the reduction in cell viability. RNA affinity purification mass spectrometry analysis identified CRIP2 as main protein interaction partner. Furthermore, SARRAH associ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research

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In conclusion, these results suggested that autophagy dysfunction-mediated necroptosis mechanistically contributed to loss of cardiomyocytes, adverse ventricular remodeling and progressive heart failure after myocardial Infarction. Inhibition of necroptosis might be the potential target for preventing post-infarction cardiac remodeling and heart failure. PMID: 32179044 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research
ConclusionsOur data demonstrate that CXCR7 suppression inhibits macrophages M1 polarization, chemotaxis and inflammation to ameliorate post-MI injury, providing novel insights and promising therapy approaches in post-MI treatment.
Source: Inflammation Research - Category: Research Source Type: research
Conclusions: We demonstrate for the first time that N-cadherin overexpression enhances MSC protective effects against IHF via β-catenin mediated MMP-10/MMP-13/HGF expression and production, promoting ADSC/cardiomyocyte adhesion and ADSC retention. PMID: 32079489 [PubMed - as supplied by publisher]
Source: Circulation Research - Category: Cardiology Authors: Tags: Circ Res Source Type: research
Discussion of the Evolutionary Genetics of Aging Thymic Involution Contributes to Immunosenescence and Inflammaging The Potential for Exosome Therapies to Treat Sarcopenia Correlations of Mitochondrial DNA Copy Number and Epigenetic Age Measures Evidence for PASK Deficiency to Reduce the Impact of Aging in Mice The Aging Retina, a Mirror of the Aging Brain Evidence for Loss of Capillary Density to be Important in Heart Disease Aspects of Immune System Aging Proceed More Rapidly in Men Deacetylation of the NLRP3 Inflammasome as a Way to Control Chronic Inflammation Transplantation of Senescent Cells is an ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Telomerase gene therapy is considered in some quarters to be a viable treatment for aging. Telomeres are the caps of repeated DNA sequences at the ends of chromosomes. They are an important part of the mechanism limiting the number of times that somatic cells in the body can divide, the Hayflick limit. A little telomere length is lost with each cell division, and short telomeres trigger cellular senescence or programmed cell death, halting replication. Stem cell populations use telomerase to lengthen their telomeres and thus self-renew to provide a continual supply of new somatic daughter cells with long telomeres to repla...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
In conclusion, high-dose NR induces the onset of WAT dysfunction, which may in part explain the deterioration of metabolic health. Towards a Rigorous Definition of Cellular Senescence The accumulation of lingering senescent cells is a significant cause of aging, disrupting tissue function and generating chronic inflammation throughout the body. Even while the first senolytic drugs capable of selectively destroying these cells already exist, and while a number of biotech companies are working on the productio...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
CRM1 (chromosomal maintenance 1) inhibitor displays anti-hypertrophy effect and controls protein trayfficking between nucleus and ctoplasm. PGC-1α is a kind of transcriptional factor co-activator which residing in nucleus predominantly and was down-regulated during heart failure. NT-PGC-1α is an alternative splicing variant of PGC-1α, which primarily distributes in cytoplasm. We hypothesis that shuttling NT-PGC-1α into nucleus by CRM1 inhibitor would probably active downstream targets of PGC-1α in nucleus and improve cardiac function in myocardial infarction mice. PGC-1α and NT-PGC-1&alp...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Abstract Heart failure with reduced ejection fraction (HFREF) increases neutral sphingomyelinase (NSMase) activity, mitochondrial reactive oxygen species emission (ROS), and causes diaphragm weakness. We tested whether a systemic pharmacologic NSMase inhibitor or short-hairpin RNA (shRNA) targeting NSMase isoform 3 (NSMase3) would prevent diaphragm abnormalities induced by HFREF caused by myocardial infarction. In the pharmacological intervention, we used intraperitoneal injection of GW4869 or vehicle. In the genetic intervention, we injected adeno-associated virus serotype 9 (AAV9) containing targeting NSMase3 or...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research
Conclusion: Taken together, our study elucidated the role and mechanism of PFL in cardiac fibrosis, indicating the potential role of PFL inhibition as a novel therapy for cardiac fibrosis.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
Abstract Hepatocyte growth factor (HGF) alleviates acute and chronic inflammation in experimental inflammatory bowel disease, glomerulonephritis, and airway inflammation. However, the anti-inflammatory effects of HGF on myocardial infarction are not defined. The current study assessed the anti-inflammatory effects of HGF in post-ischemic heart failure. The left anterior descending coronary artery was ligated in rats, and adenovirus containing human HGF (Ad-HGF) or control virus (Ad-GFP) was administered intramyocardially. The quantity of proinflammatory cytokines secreted by cardiomyocytes, such as tumor necrosis ...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
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