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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/H1003    most recent 00896.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Barrick, C. J. Articles by Smyth, S. S. PubMed PubMed Citation Articles by Barrick, C. J. Articles by Smyth, S. S.

Parent-of-origin effects on cardiac response to pressure overload in mice

¹Curriculum in Toxicology and ²Department of Genetics, Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina; and ³Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, ⁴Department of Biological Sciences, Eastern Kentucky University, and ⁵Department of Veterans Affairs Medical Center, Lexington, Kentucky

Submitted 14 August 2008 ; accepted in final form 9 June 2009

Left ventricular (LV) hypertrophy (LVH) is an independent risk factor for cardiovascular mortality and is commonly caused by hypertension. In rodents, transverse aortic constriction (TAC) is a model regularly employed in mechanistic studies of the response of the LV to pressure overload. We previously reported that inbred strains of male mice manifest different cardiac responses to TAC, with C57BL/6J (B6) developing LV dilatation and impaired contractility and 129S1/SvImJ (129) males displaying concentric LVH. In the present study, we investigated sex and parent-of-origin effects on the response to TAC by comparing cardiac function, organ weights, expression of cardiac hypertrophy markers, and histology in female B6 and female 129 mice and in F1 progeny of reciprocal crosses between B6 and 129 mice (B6129F1 and 129B6F1). Five weeks after TAC, heart weight increased to the greatest extent in 129B6F1 mice and the least extent in 129 and B6129F1 mice. Female 129B6F1 and B6 mice were relatively protected from the increase in heart weight that occurs in their male counterparts with pressure overload. The response to TAC in 129 consomic mice bearing the B6 Y chromosome resembled that of 129 rather than 129B6F1 mice, indicating that the B6 Y chromosome does not account for the differences in the reciprocal cross. Our results suggest that susceptibility to LVH is more complex than simple Mendelian inheritance and that parental origin effects strongly impact the LV response to TAC in these commonly used inbred strains.

left ventricular hypertrophy; imprinting; cardiac fibrosis; transaortic constriction