lncRNA NBR2 attenuates angiotensin II-induced myocardial hypertrophy through repressing ER stress via activating LKB1/AMPK/Sirt1 pathway

Abstract

Myocardial hypertrophy leads to heart failure (HF), and emerging researchers have illustrated that long noncoding RNAs (lncRNAs) modulate myocardial hypertrophy. Here, we explored the role and mechanism of a novel lncRNA, NBR2, in modulating angiotensin II (Ang II)-induced myocardial hypertrophy. First, we examined plasma NBR2 levels in 25 patients with HF and myocardial hypertrophy and ten healthy donors and analyzed the correlation between NBR2 profiles and patients’ clinical indicators. In addition, the overexpression experiment of NBR2 was carried out to probe the influence of NBR2 on myocardial hypertrophy. lncRNA NBR2 was down-regulated in plasma of patients with HF and myocardial hypertrophy (vs. healthy controls), and its level was negatively correlated with cardiac function (represented by left ventricular end-diastolic diameter and left ventricular ejection fraction) and degree of myocardial hypertrophy. Besides, Ang II treatment intensified the hypertrophy of human myocardial cell lines (HCM and AC16) and curbed the NBR2 expression. Overexpressing lncRNA NBR2 alleviated Angiotension II–induced myocardial hypertrophy and declined the profiles of hypertrophic markers. Moreover, up-regulating lncRNA NBR2 weakened Ang II-mediated endoplasmic reticulum (ER) stress and activated the LKB1/AMPK/Sirt1 pathway. Interfering with the LKB1/AMPK/Sirt1 axis abated the lncRNA NBR2-mediated inhibitory effect on myocardial hypertrophy and ER stress. This study confirmed that lncRNA NBR2 dampened myocardial hypertrophy and ER stress by modulating the LKB1/AMPK/Sirt1 pathway. Our study provides the first evidence that lncRNA NBR2 is positively associated with myocardial hypertrophy.

Dronedarone Attenuates Ang II-Induced Myocardial Hypertrophy Through Regulating SIRT1/FOXO3/PKIA Axis

“…At present, SIRT1 was investigated in MH progression. For example, Zhu et al 28) reported that SIRT1 was evidently decreased by Ang II induction and lncRNA NBR2 activated LKB1/AMPK/SIRT1 pathway to repress endoplasmic reticulum stress, thereby attenuating Ang II-induced MH. Ginsenoside Rg3 upregulated SIRT1 to suppress Ang II-induced MH through inhibiting NLRP3 inflammasome and oxidative stress.…”

Bioinformatics and Experimental Analyses Reveal Immune-Related LncRNA–mRNA Pair AC011483.1-CCR7 as a Biomarker and Therapeutic Target for Ischemic Cardiomyopathy

“…In various human cancers, the expression of NBR2 is dysregulated and associated with clinical outcomes [ 34 , 35 , 36 ]. Moreover, one study provided the first evidence that NBR2 is relevant with myocardial hypertrophy by finding that NBR2 inhibits endoplasmic reticulum (ER) stress and myocardial hypertrophy by modulating the LKB1/AMPK/Sirt1 pathway [ 37 ]. C3orf35 , also known as APRG1 , was associated with poor prognosis of osteosarcoma and may affect tumor metastasis and immune cell infiltration in osteosarcoma patients [ 38 ].…”

Chlorogenic acid attenuates cardiac hypertrophy via up‐regulating Sphingosine‐1‐phosphate receptor1 to inhibit endoplasmic reticulum stress

“…18,19 What is more, it has been reported that long non-coding RNA (lncRNA) NBR2 could attenuate angiotensin II-induced myocardial hypertrophy by reducing ERS through activating the LKB1/AMPK/SIRT1 pathway. 20 Therefore, we speculate that AMPK/SIRT1 signalling may be implicated in the mediation of cardiac hypertrophy by CGA.…”

“…Sirtuin 1 (SIRT1) has been shown to protect hearts against ERS‐induced cell death, and impairment of the cardiac SIRT1 signalling contributes to the pathogenesis of cardiovascular diseases 18,19 . What is more, it has been reported that long non‐coding RNA (lncRNA) NBR2 could attenuate angiotensin II‐induced myocardial hypertrophy by reducing ERS through activating the LKB1/AMPK/SIRT1 pathway 20 . Therefore, we speculate that AMPK/SIRT1 signalling may be implicated in the mediation of cardiac hypertrophy by CGA.…”