Heart failure-inducible gene therapy targeting protein phosphatase 1 prevents progressive left ventricular remodeling.

PloS One
Yosuke MiyazakiMasunori Matsuzaki

Abstract

The targeting of Ca(2+) cycling has emerged as a potential therapy for the treatment of severe heart failure. These approaches include gene therapy directed at overexpressing sarcoplasmic reticulum (SR) Ca(2+) ATPase, or ablation of phospholamban (PLN) and associated protein phosphatase 1 (PP1) protein complexes. We previously reported that PP1β, one of the PP1 catalytic subunits, predominantly suppresses Ca(2+) uptake in the SR among the three PP1 isoforms, thereby contributing to Ca(2+) downregulation in failing hearts. In the present study, we investigated whether heart-failure-inducible PP1β-inhibition by adeno-associated viral-9 (AAV9) vector mediated gene therapy is beneficial for preventing disease progression in genetic cardiomyopathic mice. We created an adeno-associated virus 9 (AAV9) vector encoding PP1β short-hairpin RNA (shRNA) or negative control (NC) shRNA. A heart failure inducible gene expression system was employed using the B-type natriuretic protein (BNP) promoter conjugated to emerald-green fluorescence protein (EmGFP) and the shRNA sequence. AAV9 vectors (AAV9-BNP-EmGFP-PP1βshRNA and AAV9-BNP-EmGFP-NCshRNA) were injected into the tail vein (2×10(11) GC/mouse) of muscle LIM protein deficient mice (MLPKO), f...Continue Reading

References

Aug 1, 1993·Cardiovascular Drugs and Therapy·J M Cruickshank
Jan 1, 1997·Journal of Molecular and Cellular Cardiology·J NeumannN Zimmermann
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·M I MiyamotoR J Hajjar
Jan 24, 2002·Nature·Donald M Bers
Jun 12, 2003·Journal of the American College of Cardiology·Alan S MaiselUNKNOWN Breathing Not Properly Multinational Study Investigators
Sep 23, 2003·The Journal of Thoracic and Cardiovascular Surgery·Danny ChuPatricia A Thistlethwaite
Apr 22, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Michio YamadaMasunori Matsuzaki
Jul 29, 2006·Circulation Research·Christina A PacakBarry J Byrne
Oct 13, 2006·The Journal of Cell Biology·Michinori ToriyamaNaoyuki Inagaki
Nov 7, 2006·Journal of the American College of Cardiology·Masahiko HoshijimaKenneth R Chien
Feb 13, 2008·Physiology·Yasuhiro IkedaKenneth R Chien
Apr 5, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kazuo NiwanoMasahiko Kurabayashi
Jul 22, 2009·The Journal of Clinical Investigation·Katsuhisa MatsuuraIssei Komuro
Jul 30, 2010·Heart·Matthew J Lovell, Anthony Mathur
Nov 16, 2010·Archives of Cardiovascular Diseases·Mario T Njeim, Roger J Hajjar
Nov 26, 2010·Journal of Molecular and Cellular Cardiology·Judith K GwathmeyRoger J Hajjar
Dec 2, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Lauren E Mays, James M Wilson
Feb 8, 2011·The American Journal of Medicine·Catherine Y WongHarlan M Krumholz
Mar 1, 2011·Cardiovascular Research·Katrin WittköpperAli El-Armouche
May 18, 2011·The Journal of Clinical Investigation·Christie L BellJames M Wilson
Jun 29, 2011·Circulation·Mariell JessupUNKNOWN Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) Investigators

❮ Previous
Next ❯

Citations

Nov 25, 2014·Global Cardiology Science & Practice·Georgia KalozoumiDespina Sanoudou
Sep 23, 2014·Journal of Molecular and Cellular Cardiology·Hiroki SakaiMakoto Inui
Oct 13, 2015·Journal of Molecular and Cellular Cardiology·Kobra HaghighiEvangelia G Kranias
Sep 21, 2013·Journal of Molecular and Cellular Cardiology·Jordi HeijmanDobromir Dobrev
May 16, 2018·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Gang LiuXiao Yong Tong
Nov 8, 2013·American Journal of Physiology. Cell Physiology·Chao HuangWei Zhang
Mar 22, 2019·Frontiers in Cardiovascular Medicine·Rajinikanth GogirajuKatrin Schäfer
Jun 8, 2017·Heart Failure Reviews·Abesh Bera, Dwaipayan Sen

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
transfections
transgenic
PCR

Software Mentioned

Ionoptix
SigmaScanPro
SarcLen

Related Concepts

Related Feeds

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.

Cardiac Remodeling

Cardiac remodeling in response to a myocardial infarction is characterized by progressive ventricular dilatation, cardiac hypertrophy, fibrosis, and deterioration of cardiac performance. Discover the latest research on Cardiac Remodeling here.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.