Increased B-type-natriuretic peptide promotes myocardial cell apoptosis via the B-type-natriuretic peptide/long non-coding RNA LSINCT5/caspase-1/interleukin 1β signaling pathway.
Chronic heart failure (CHF) is the final stage of various heart diseases, and is increasingly recognized as a major health problem in the elderly. Previous studies demonstrated that B‑type‑natriuretic peptide (BNP) is an established biomarker of CHF. Furthermore, BNP also regulates cell proliferation, differentiation and apoptosis. Recent evidence has revealed that BNP affects myocardial cell apoptosis during myocardial ischemia‑reperfusion injury. Long non‑coding RNAs (lncRNAs) are emerging as novel molecular compounds involved in gene regulation, and have important roles in numerous human diseases. However, the mechanism underlying the BNP and lncRNA-induced regulation of myocardial cell apoptosis remains to be elucidated. The present study reported that lncRNA LSINCT5, upregulated by BNP, is able to regulate myocardial cell apoptosis via the activation of the caspase‑1/interleukin (IL)‑1β signaling pathway. BNP-induced apoptosis of HCM cells was observed using flow cytometry, and involved caspase‑1. In addition, expression profiling using a human lncRNA polymerase chain reaction array revealed that LSINCT5 was highly expressed in BNP-treated myocardial cells, as compared with untreated cells. The role of lncRNA LSINCT5 in HCM cell apoptosis was also investigated. The results of the present study indicated that LSINCT5 silencing by small interfering RNA inhibits caspase‑1/IL‑1β signaling, and suppresses apoptosis in BNP-treated HCM cells. Therefore, high expression levels of BNP promote the apoptosis of myocardial cells through the lncRNA LSINCT5 mediator, which activates the caspase‑1/IL‑1β signaling pathway. These findings uncovered a novel pathogenic mechanism, and provided a potential therapeutic target for CHF.
Department of Geriatrics, Shanghai First People's Hospital, Shanghai 200080, P.R. China.
Xian
X
Zhang
Department of Geriatrics, Shanghai First People's Hospital, Shanghai 200080, P.R. China.
Minglei
M
Sha
Department of Geriatrics, Shanghai First People's Hospital, Shanghai 200080, P.R. China.
Yuting
Y
Yao
Department of Geriatrics, Shanghai First People's Hospital, Shanghai 200080, P.R. China.
Jia
J
Da
Department of Geriatrics, Shanghai First People's Hospital, Shanghai 200080, P.R. China.
Dadao
D
Jing
D017209:Apoptosis; D020170:Caspase 1 / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000502:physiology*; D020097:Natriuretic Peptide, Brain / Q000502:physiology*; D034622:RNA Interference; D062085:RNA, Long Noncoding; D015398:Signal Transduction
D053583:Interleukin-1beta; D062085:RNA, Long Noncoding; D020097:Natriuretic Peptide, Brain; D020170:Caspase 1