Model of functional cardiac aging: young adult mice with mild overexpression of serum response factor.
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 approximately 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.
Zhang
Xiaomin
X
Reynolds Center on Aging, Dept. of Geriatrics, Univ. of Arkansas for Medical Science, 4301 West Markham Ave., Slot 748, Little Rock, AR 72205, USA. weijeanne@uams.edu
Azhar
Gohar
G
Furr
Maxwell C
MC
Zhong
Ying
Y
Wei
Jeanne Y
JY
D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D015150:Echocardiography, Doppler; D015870:Gene Expression; D006321:Heart / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009206:Myocardium / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D026362:Serum Response Factor / Q000235:genetics*; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000473:pathology
D012333:RNA, Messenger; D026362:Serum Response Factor