Back to Search
Start Over
Ca2+-independent positive molecular inotropy for failing rabbit and human cardiac muscle by alpha-myosin motor gene transfer.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2010 Feb; Vol. 24 (2), pp. 415-24. Date of Electronic Publication: 2009 Oct 02. - Publication Year :
- 2010
-
Abstract
- Current inotropic therapies used to increase cardiac contractility of the failing heart center on increasing the amount of calcium available for contraction, but their long-term use is associated with increased mortality due to fatal arrhythmias. Thus, there is a need to develop and explore novel inotropic therapies that can act via calcium-independent mechanisms. The purpose of this study was to determine whether fast alpha-myosin molecular motor gene transfer can confer calcium-independent positive inotropy in slow beta-myosin-dominant rabbit and human failing ventricular myocytes. To this end, we generated a recombinant adenovirus (AdMYH6) to deliver the full-length human alpha-myosin gene to adult rabbit and human cardiac myocytes in vitro. Fast alpha-myosin motor expression was determined by Western blotting and immunocytochemical analysis and confocal imaging. In experiments using electrically stimulated myocytes from ischemic failing hearts, AdMYH6 increased the contractile amplitude of failing human [23.9+/-7.8 nm (n=10) vs. AdMYH6 amplitude 78.4+/-16.5 nm (n=6)] and rabbit myocytes. The intracellular calcium transient amplitude was not altered. Control experiments included the use of a green fluorescent protein or a beta-myosin heavy chain adenovirus. Our data provide evidence for a novel form of calcium-independent positive inotropy in failing cardiac myocytes by fast alpha-myosin motor protein gene transfer.
- Subjects :
- Animals
Cardiac Myosins genetics
Cloning, Molecular
Disease Models, Animal
Gene Transfer Techniques
Humans
Myocardial Ischemia physiopathology
Myocardium metabolism
Myocytes, Cardiac drug effects
Myocytes, Cardiac physiology
Myosin Heavy Chains genetics
Rabbits
Stimulation, Chemical
Calcium metabolism
Myocardial Contraction physiology
Ventricular Myosins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 24
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 19801488
- Full Text :
- https://doi.org/10.1096/fj.09-140566