コンテンツメニュー

Yano Masafumi


Heart failure-inducible suppression of protein phosphatase 1β partially prevents cardiac remodeling in experimental pressure overload-induced heart failure

The bulletin of the Yamaguchi Medical School Volume 64 Issue 1-2 Page 1-12
published_at 2017
A050064000101.pdf
[fulltext] 2.05 MB
Title
Heart failure-inducible suppression of protein phosphatase 1β partially prevents cardiac remodeling in experimental pressure overload-induced heart failure
Abstract
Aberrant increases in protein phosphatase 1(PP1) activity have been shown to be associated with inefficient sarcoplasmic reticulum Ca^{2+} cycling, leading to cardiac dysfunction in the failing heart. In the present study, we investigated whether BNP promoter-inducible suppression of PP1β would ameliorate progression of pressure overload-induced heart failure in mice, a clinically relevant animal model. An Adeno-associated virus 9 (AAV9) vector encoding PP1βshRNA and a negative control (NC) shRNA driven by a brain natriuretic peptide (BNP) promoter with an emerald green fluorescent protein expression (EmGFP) cassette were used to test the hypothesis. AAV9 vectors (AAV9-BNP-EmGFP-PP1βshRNA and AAV9-BNP-EmGFP-NCshRNA) were introduced into the in vivo heart via the tail vein injection (4x10^{11} GC/mice) in 8-week-old C57BL6J mice, followed by transverse aortic constriction (TAC) 2 weeks after the AAV9 vector injection. Post TAC cardiac function was sequentially assessed every 2 week by echocardiography, followed by hemodynamic assessment at 1 month. AAV9-BNP-EmGFP-PP1βshRNA treatment suppressed myocardial PP1β expression by 15% compared with the NCshRNA group (p<0.001). The fractional shortening (%FS) of the left ventricle in the PP1βshRNA-treated group was significantly larger than the NCshRNA-treated group (21%±1.0% vs. 15%±0.01, p<0.01). The ratios of heart weight (HW) / body weight (BW) and lung weight (LW) / BW in the PP1βshRNA group were significantly smaller than those of the NCshRNA group (HW/BW: 9.20±0.49 vs. 10.6±0.45 mg/g
Creators Shiraishi Kozo
Creators Ikeda Yasuhiro
Creators Miyazaki Yosuke
Creators Fujimoto Shizuka N.
Creators Yoshimura Koichi
Creators Miura Toshiro
Creators Matsuzaki Masanori
Affiliate Master Yamaguchi University
[kakenhi]15501 grid.268397.1
Creators Yano Masafumi
Source Identifiers [PISSN] 0513-1812 [NCID] AA00594272
Creator Keywords
protein phosphatase 1β(PP1β) adeno-associated virus 9 (AAV9) vector brain natriuretic peptide (BNP) promoter AAV9-BNP-EmGFP-PP1βshRNA transverse aortic constriction (TAC)
Languages eng
Resource Type departmental bulletin paper
Publishers Yamaguchi University School of Medicine
Date Issued 2017
File Version Version of Record
Access Rights open access
Schools 大学院医学系研究科(医学)