Decreased beta-adrenergic responsiveness following hypertrophy occurs only in cardiomyocytes that also re-express beta-myosin heavy chain.

Abstract

AIMS:

Cardiac hypertrophy is associated with a reduction in the contractile response to beta-adrenergic stimulation, and with re-expression of foetal genes such as beta-myosin heavy chain (MHC). However, whether these two markers of pathology develop concordantly in the same individual cells or independently in different cells is not known.

METHODS AND RESULTS:

To answer this question, we examined the beta-adrenergic response of individual beta-MHC expressing and non-expressing myocytes from hypertrophic hearts, using a previously generated mouse model (YFP/beta-MHC) in which a yellow fluorescent protein (YFP) is fused to the native beta-MHC protein allowing easy identification of beta-MHC expressing cells. Yellow fluorescent protein/beta-MHC mice were submitted to 4 weeks of transverse aortic constriction (TAC), and the contractile parameters of isolated individual myocytes in response to the beta-adrenergic agonist isoproterenol were assessed. Our results demonstrate that the decrease in isoproterenol-induced cell shortening that develops in TAC hearts occurs only in those hypertrophic myocytes that re-express beta-MHC. Hypertrophic myocytes that do not express beta-MHC have contractility indices indistinguishable from non-TAC controls.

CONCLUSION:

These data show that the reduction of beta-adrenergic response occurs only in subsets, rather than in all myocytes, and is coincident with re-expression of beta-MHC.

• Authors: Kumar Pandya, Kristine Porter, Howard A Rockman, Oliver Smithies
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 11 Issue 7 Pg. 648-52 (Jul 2009) ISSN: 1388-9842 [Print] England
• PMID: 19553396 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Agonists
• Receptors, Adrenergic, beta
• Myosin Heavy Chains
• Isoproterenol

Topics

• Adrenergic beta-Agonists (metabolism, pharmacology)
• Animals
• Cardiomegaly (diagnostic imaging, metabolism, physiopathology)
• Cardiomyopathies (diagnostic imaging, metabolism, physiopathology)
• Disease Models, Animal
• Isoproterenol (metabolism, pharmacology)
• Mice
• Myocardial Contraction (drug effects)
• Myocardium (cytology, metabolism)
• Myosin Heavy Chains (biosynthesis)
• Receptors, Adrenergic, beta (metabolism)
• Ultrasonography