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Parvalbumin gene delivery improves diastolic function in the aged myocardium in vivo
Journal article   Open access   Peer reviewed

Parvalbumin gene delivery improves diastolic function in the aged myocardium in vivo

Daniel E Michele, Michael L Szatkowski, Faris P Albayya and Joseph M Metzger
Molecular therapy, v 10(2), pp 399-403
Aug 2004
PMID: 15294186
url
https://doi.org/10.1016/j.ymthe.2004.05.011View
Published, Version of Record (VoR)CC BY-NC-ND V4.0 Open

Abstract

Adenoviridae - genetics Age Factors Animals Cardiac Output, Low - genetics Cardiac Output, Low - therapy Diastole Gene Transfer Techniques Genetic Therapy - methods Myocardium - chemistry Myocardium - metabolism Myocytes, Cardiac - metabolism Parvalbumins - analysis Parvalbumins - genetics Parvalbumins - metabolism Rats
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.

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Web of Science research areas
Biotechnology & Applied Microbiology
Genetics & Heredity
Medicine, Research & Experimental
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