Long Non-Coding RNA Malat-1 Is Dispensable during Pressure Overload-Induced Cardiac Remodeling and Failure in Mice

• Published in: PloS one 2016-02, Vol.11 (2), p.e0150236
• Main Authors: Peters, Tim, Hermans-Beijnsberger, Steffie, Beqqali, Abdelaziz, Bitsch, Nicole, Nakagawa, Shinichi, Prasanth, Kannanganattu V, de Windt, Leon J, van Oort, Ralph J, Heymans, Stephane, Schroen, Blanche
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Adenocarcinoma; Alternative splicing; Angiotensin; Angiotensin II; Angiotensin II - metabolism; Angiotensin II - toxicity; Animals; Aorta; Aorta, Thoracic; Biology and Life Sciences; Cancer; Cardiology; Cardiomegaly - etiology; Cardiomegaly - genetics; Cardiomyocytes; Cardiomyopathy; Cardiovascular diseases; Constriction, Pathologic - complications; Crosses, Genetic; Development and progression; Developmental biology; Diabetes; Embryogenesis; Embryonic growth stage; Eutrophication; Fetal Proteins - biosynthesis; Fetal Proteins - genetics; Fibrosis; Gene expression; Gene Expression Regulation - genetics; Genetic aspects; Genotypes; Heart; Heart diseases; Heart failure; Heart Failure - etiology; Heart Failure - genetics; Heterozygote; Hypertension; Hypertrophy; Hypoxia; Infiltration; Ligation; Lung cancer; Lungs; MAP kinase; Medical research; Medicine and Health Sciences; Metastases; Metastasis; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; MicroRNA; MicroRNAs; miRNA; Non-coding RNA; Physiological aspects; Pressure; Proteins - genetics; Proteins - metabolism; Research and Analysis Methods; Ribonucleic acid; RNA; RNA Splicing - genetics; RNA, Long Noncoding - genetics; RNA, Long Noncoding - physiology; Rodents; Thorax; Tibia; Transcription; Vascularization; Ventricle; Ventricular Remodeling - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0150236

Long non-coding RNAs (lncRNAs) are a class of RNA molecules with diverse regulatory functions during embryonic development, normal life, and disease in higher organisms. However, research on the role of lncRNAs in cardiovascular diseases and in particular heart failure is still in its infancy. The exceptionally well conserved nuclear lncRNA Metastasis associated in lung adenocarcinoma transcript 1 (Malat-1) is a regulator of mRNA splicing and highly expressed in the heart. Malat-1 modulates hypoxia-induced vessel growth, activates ERK/MAPK signaling, and scavenges the anti-hypertrophic microRNA-133. We therefore hypothesized that Malat-1 may act as regulator of cardiac hypertrophy and failure during cardiac pressure overload induced by thoracic aortic constriction (TAC) in mice. Absence of Malat-1 did not affect cardiac hypertrophy upon pressure overload: Heart weight to tibia length ratio significantly increased in WT mice (sham: 5.78±0.55, TAC 9.79±1.82 g/mm; p