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J Cell Biochem. 2018 Feb;119(2):1804-1818. doi: 10.1002/jcb.26341. Epub 2017 Sep 18.

Effects of gene knockdown of CNP on ventricular remodeling after myocardial ischemia-reperfusion injury through NPRB/Cgmp signaling pathway in rats.

Author information

1
Department of Cardiac Surgery, Jining No.1 People's Hospital, Jining, China.
2
Department of Cardiology, Dongying City People's Hospital, Dongying, China.

Abstract

This study aimed to explore effects of CNP on ventricular remodeling following myocardial ischemia-reperfusion (I/R) injury through the NPRB/cGMP signaling pathway. Rat cardiomyocytes were assigned into: control, I/R, I/R + CNP, and I/R + 8-Br-cGMP groups. ELISA, qRT-PCR, and Western blotting were used to detect cGMP content and expression, respectively. After model establishment of I/R rats, normal control, CNP-/- control, I/R, and CNP-/- groups were set. Indexes of heart were detected using echocardiography and hemodynamics. ELISA was used to measure serum CNP, cGMP, LDH, cTn I, CK-MB, TNF-α, and IL-6 levels. Myocardial infarct was identified by TTC staining, and apoptosis conditions by TUNEL staining. QRT-PCR and Western blotting were adopted to detect expressions of CNP, NPRB, cGMP, and apoptosis-related genes. Compared with control group, cGMP contents and expression in the I/R, I/R + CNP and I/R + 8-Br-cGMP groups were decreased. Levels of LVEDV, LVESV, LVDS, LVDD, IVSD, LVM, LVEDP, and LVSP were higher in the I/R, CNP-/- control, and CNP-/- groups than normal control group while LVEF, SV, CO, and ±dp/dtmax were lower. Compared with the normal control group, LDH, cTn I, CK-MB, TNF-α, and IL-6 were higher in the I/R, CNP-/- control and CNP-/- groups; pathological changes and myocardial infarction were observed in the I/R, CNP-/- control, and CNP-/- groups; expressions of apoptosis-related genes in those groups were higher; while CNP, NPRB, cGMP, and Bcl-2 expressions were decreased. We came to the conclusion that gene knockdown of CNP blocks the NPRB/cGMP signaling pathway, thereby aggravating myocardial I/R injury and causing ventricular remodeling in rats.

KEYWORDS:

C-type natriuretic peptide; NPRB/cGMP signaling pathway; gene knockdown; myocardial ischemia-reperfusion injury; ventricular remodeling

PMID:
28796407
DOI:
10.1002/jcb.26341
[Indexed for MEDLINE]

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