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Am J Physiol Regul Integr Comp Physiol 285: R552-R560, 2003; doi:10.1152/ajpregu.00631.2002
0363-6119/03 $5.00
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REGULATION IN GENETICALLY MODIFIED ANIMALS

Model of functional cardiac aging: young adult mice with mild overexpression of serum response factor

Xiaomin Zhang,* Gohar Azhar,* Maxwell C. Furr, Ying Zhong, and Jeanne Y. Wei

Reynolds Center on Aging, Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205

Submitted 11 October 2002 ; accepted in final form 23 May 2003

Serum response factor (SRF) is an important transcription factor that may have a role in the maintenance of cardiac structure and function. The level of SRF mRNA expression increases ~16% in the hearts of mice during adult aging. To model the effect of mild SRF elevation in the aging heart, transgenic mice with low levels of SRF overexpression were generated. By 6 mo of age, the transgenic mice had a 19% increase of heart-to-body weight ratio compared with nontransgenic mice. In addition, they had a 12% increase in myocyte size, a 6.7% increase in collagen deposition, and altered gene expression of a number of muscle-specific and cardiac genes. Doppler echocardiography revealed that these transgenic mice had increased left ventricular wall thickness and decreased left ventricular (LV) volumes, increased LV stiffness with 20% reduction in early diastolic LV filling (peak E), and 35% decline in peak E-to-peak A (late diastolic filling) ratio. The observed changes, especially those in the E/A ratio, are similar to those seen clinically in late life as a part of human adult myocardial aging.

transcription factor; transgenic; cardiac structure and function


Address for reprint requests and other correspondence: J. Wei, Reynolds Center on Aging, Dept. of Geriatrics, Univ. of Arkansas for Medical Science, 4301 West Markham Ave., Slot 748, Little Rock, AR 72205 (E-mail: weijeanne{at}uams.edu).






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