The Expression of microRNA in Adult Rat Heart with Isoproterenol-Induced Cardiac Hypertrophy

Abstract

Cardiac hypertrophy is a common pathological condition and an independent risk factor that triggers cardiovascular morbidity. As an important epigenetic regulator, miRNA is widely involved in many biological processes. In this study, miRNAs expressed in rat hearts that underwent isoprenaline-induced cardiac hypertrophy were identified using high-throughput sequencing, and functional verification of typical miRNAs was performed using rat primary cardiomyocytes. A total of 623 miRNAs were identified, of which 33 were specifically expressed in cardiac hypertrophy rats. The enriched pathways of target genes of differentially expressed miRNAs included the FoxO signaling pathway, dopaminergic synapse, Wnt signaling pathway, MAPK (mitogen-activated protein kinase) signaling pathway, and Hippo signaling pathway. Subsequently, miR-144 was the most differentially expressed miRNA and was subsequently selected for in vitro validation. Inhibition of miR-144 expression in primary myocardial cells caused up-regulation of cardiac hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). The dual luciferase reporter system showed that ANP may be a target gene of miR-144. Long non-coding RNA myocardial infarction associated transcript (LncMIAT) is closely related to heart disease, and here, we were the first to discover that LncMIAT may act as an miR-144 sponge in isoproterenol-induced cardiac hypertrophy. Taken together, these results enriched the understanding of miRNA in regulating cardiac hypertrophy and provided a reference for preventing and treating cardiac hypertrophy.

Naringenin Attenuates Isoprenaline-Induced Cardiac Hypertrophy by Suppressing Oxidative Stress through the AMPK/NOX2/MAPK Signaling Pathway

“…The excessive ROS derived from NADPH oxidases activates various hypertrophy-related signaling pathways, for example, the MAPK signaling pathway [ 43 ]. Treatment with ISO has been reported to activate the MAPK signaling pathway [ 44 ], composed of P38, JNK, and ERK. The signaling pathway regulates a variety of biological behaviors, including cell proliferation, differentiation, and apoptosis [ 45 ].…”

Inflammatory Forms of Cardiomyocyte Cell Death in the Rat Model of Isoprenaline-Induced Takotsubo Syndrome

“…The pathological increase in the concentration of circulating catecholamines and their excessive release from the cardiac sympathetic nerve endings lead to direct damage to the cardiomyocytes [30]. The pathophysiological mechanisms involved in catecholamineinduced myocardial injury include increased oxygen demand of the cardiomyocytes with insufficient supply, oxidative stress, calcium overload, myofibril over-contraction, and upregulation of the expression and release of inflammatory cytokines [31][32][33][34][35][36][37][38][39][40][41][42]. Indeed, histopathological examinations of the myocardium of rats treated with supraphysiological doses of catecholamines showed focal necrosis and degeneration of the cardiomyocytes, disordered myofibrils, advanced cytoplasmic vacuolization, myocardial infiltration with inflammatory cells, and tissue fibrosis [43][44][45].…”

Non-coding RNAs as regulators of the Hippo pathway in cardiac development and cardiovascular disease

“…The knockout of LATS1/2 in the epicardium of mouse embryos is embryonically lethal, resulting in defective coronary arteries ( Singh et al, 2016 ; Xiao et al, 2018 ). Gan M. et al (2020) reported that p-LATS1/2 inhibits mTORC1 signaling to control heart size by directly phosphorylating S606 of Raptor to attenuate mTORC1 kinase activation.…”