Undernutritionin UteroAugments Systolic Blood Pressure and Cardiac Remodeling in Adult Mouse Offspring: Possible Involvement of Local Cardiac Angiotensin System in Developmental Origins of Cardiovascular Disease

Makoto Kawamura, Hiroaki Itoh, Shigeo Yura, Haruta Mogami, Shin-Ichi Suga, Hisashi Makino, Yoshihiro Miyamoto, Yasunao Yoshimasa, Norimasa Sagawa, Shingo Fujii
2007 Endocrinology  
Evidence has emerged that undernutrition in utero is a risk factor for cardiovascular disorders in adulthood, along with genetic and environmental factors. Recently, the local expression of angiotensinogen and related bioactive substances has been demonstrated to play a pivotal role in cardiac remodeling, i.e. fibrosis and hypertrophy. The aim of the present study was to clarify the possible involvement of the local cardiac angiotensin system in fetal undernutrition-induced cardiovascular
more » ... ers. We developed a mouse model of undernutrition in utero by maternal food restriction, in which offspring (UN offspring) showed an increase in systolic blood pressure (8 wk of age, P < 0.05; and 16 wk, P < 0.01), perivas-cular fibrosis of the coronary artery (16 wk, P < 0.05) and cardiac cardiomegaly (16 wk, P < 0.01), and cardiomyocyte enlargement, concomitant with a significant augmentation of angiotensinogen (P < 0.05) and endothelin-1 (P < 0.01) mRNA expression and a tendency to increase in immunostaining for both angiotensin II and endothelin-1 in the left ventricles (16 wk). These findings suggest that fetal undernutrition activated the local cardiac angiotensin system-associated bioactive substances, which contributed, at least partly, to the development of cardiac remodeling in later life, in concert with the effects of increase in blood pressure.
doi:10.1210/en.2006-0706 pmid:17138658 fatcat:2mvpel6h2vb5rbgg7svnpqgxzu