Decreased Efficiency of Adenovirus-Mediated Gene Transfer in Aging Cardiomyocytes

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Abstract
Background— Aging is an independent risk factor for the development of cardiovascular disease. Clinical application of myocardial gene transfer may be best suited in the elderly. In vivo gene transfer by adenovirus is less efficient in aging myocardium. Methods and Results— When infected with adenovirus containing β-galactosidase (β-gal) and green fluorescent protein (GFP) driven by cytomegalovirus promoters in vitro, aging rat cardiac myocytes exhibit significantly lower infectivity and delayed transgene expression compared with adult controls. Abnormalities of viral internalization may be one mechanism accounting for this difference. To investigate this, we studied expression levels of the coxsackievirus and adenovirus receptor (CAR) as well as other potential integrins involved in the internalization of adenoviruses. CAR expression tended to be upregulated whereas among potential integrins, α3β1 was downregulated in aging cardiac myocytes. Blocking the β1 component of α3β1 further decreased infectivity...