Parvalbumin gene delivery improves diastolic function in the aged myocardium in vivo.
Abnormal relaxation of the heart, termed diastolic dysfunction, is a significant and growing problem that is a major cause of heart failure in the aged population. The potential of gene transfer of parvalbumin (Parv), a cytoplasmic calcium-binding protein, to improve diastolic function in the aged myocardium in vivo was evaluated. Despite evidence for an early developmental influence on the efficiency of Ad5 striated muscle transduction, results show that Ad5 gene transfer efficiency to adult cardiac myocytes in vitro is identical in young and old rats, suggesting that the basic processes of adenovirus binding and internalization are unaffected by aging. In contrast, Ad5-mediated Parv gene transfer to the myocardium in vivo is reduced in old rats compared to young rats. Nonetheless, Parv gene transfer and expression in vivo were sufficient to improve tau, a load-independent indicator of diastolic function, assessed using catheter-based micromanometry in the aged myocardium. These results suggest that expression of the calcium buffer Parv may represent an effective approach to functional correction of the failing heart in the aging.
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Daniel E
DE
Michele
Michael L
ML
Szatkowski
Faris P
FP
Albayya
Joseph M
JM
Metzger
D000256:Adenoviridae / Q000235:genetics; D000367:Age Factors; D000818:Animals; D002303:Cardiac Output, Low / Q000235:genetics / Q000628:therapy*; D003971:Diastole; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D010320:Parvalbumins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D051381:Rats
D010320:Parvalbumins