Diagnosis and treatment of myocardial failure

Abstract

The invention provides methods of diagnosing myocardial failure in a human. The methods comprise obtaining a sample of myocardial tissue from a ventricle of the heart of the human. In one method, the expression of α-myosin heavy chain (α-MHC), β-myosin heavy chain (β-MHC), or both in the sample is quantitated, and it is determined by statistical analysis if the expression of α-MHC, β-MHC, or both in the sample is significantly different than their expression in normal human ventricular myocardial tissue. A second method comprises quantitating the expression of α1-thyroid hormone receptor (α1-THR), α2-THR, α1-THR+β1-THR, or combinations thereof in the sample, and determining by statistical analysis if the expression of α1-THR, α2-THR, or α1-THR+β1-THR in the sample is significantly different than their expression in normal human ventricular myocardial tissue. The invention also provides kits for diagnosing myocardial failure by these methods. The invention further provides methods of treating myocardial failure in a human. One method comprises administering an effective amount of an agent that directly causes an increase in the quantity of α-MHC in the myocardial tissue of the heart. A second method comprises administering an effective amount of an agent that directly causes an increase in the quantity of α1-THR, an increase in the quantity of β1-THR, a decrease in the quantity of α2-THR, or combinations thereof, in the myocardial tissue of the heart. Finally, the invention provides a method of quantitating the expression of a first protein relative to the expression of a second protein or to the total expression of the first and second proteins. The method comprises obtaining a sample of cells or tissue expressing the first protein and the second protein, extracting RNA from the cells or tissue, preparing cDNA from the RNA, amplifying the cDNA coding for the first and second proteins by polymerase chain reaction using primers that hybridize to cDNA coding for the first protein, the second protein or both, and quantitating the amplified PCR products.

1 - 45 . (canceled)  
     
     
         46 . A method of treating myocardial failure or heart failure in a human comprising administering an effective amount of an agent that directly causes an increase in the quantity, expression or relative amount of alpha myosin heavy chain (α-MHC) in the myocardial tissue of the heart.  
     
     
         47 . The method of  claim 46 , wherein said agent is a small molecule, pharmaceutical or chemical compound.  
     
     
         48 . The method of  claim 46 , wherein treating heart failure comprises one or more of reversing cardiac remodeling, improving or reversing cardiac hypertrophy, increasing exercise capacity, increasing cardiac ejection volume, decreasing left ventricular end diastolic pressure, decreasing pulmonary capillary wedge pressure, increasing cardiac output or cardiac index, lowering pulmonary artery pressures, decreasing left ventricular end systolic and diastolic dimensions, decreasing left and right ventricular all stress, decreasing wall tension, increasing quality of life, or decreasing disease related morbidity or mortality.  
     
     
         49 . The method of  claim 46 , wherein increasing the expression of α-MHC comprises increasing the expression of α-MHC RNA.  
     
     
         50 . The method of  claim 46 , wherein increasing the expression of α-MHC comprises increasing the expression of α-MHC protein.  
     
     
         51 . The method of  claim 46 , wherein increasing the relative amount of α-MHC further comprises decreasing the amount of beta myosin heavy chain (β-MHC) in the heart.