TITLE:
Effect of gestational protein restriction on left ventricle hypertrophy and heart angiotensin II signaling pathway in adult offspring rats
AUTHORS:
Renan Brisollada Silva, Flávia Fernandes Mesquita, Marília Andreo, Heloisa Balan Assalin, José Antônio Rocha Gontijo, Patrícia Aline Boer
KEYWORDS:
Low Birth Weight; Arterial Hypertension; Fetal Programming; Protein Restriction; Angiotensin II; Left Ventricle Hypertrophy; Cardiovascular Disease
JOURNAL NAME:
Health,
Vol.5 No.4A,
April
30,
2013
ABSTRACT: Maternal protein restriction may be a risk factor for cardiovascular
disorders in adulthood. The RAS (renin-angiotensin-system) plays a pivotal role
in cardiac remodeling. Components of the RAS, including angiotensin II (AngII) and
its receptors type 1 (AT1R) and 2 (AT2R) are expressed in the heart. This study
investigates whether gestational protein restriction alters the expression and localization
of AT1R and AT2R and RAS signaling pathway proteins in parallel with left ventricle hypertrophy and systemic hypertension in male offspring. Dams were kept on normal (NP, 17% protein) or low
(LP, 6% protein) protein diet during pregnancy. Systolic blood pressure (SBP) of
male offspring was measured from the 8th to 16th week and
left ventricles of 16-wk-old rats were processed
for histology, morphometric, immunoblotting and immunohistochemistry. LP offspring showed a significant reduction in birth body weight and SBP increased significantly from the 8th week. Left ventricle mass and cardiomyocytes area were also significantly higher
in LP animals. Widespread perivascular fibrosis was not detected in the heart tissue.
Analysis by immunoblotting and immunohistochemistry demonstrated a significant enhance
in cardiomyocyte expression of AT1R and ERK1 in LP offspring. Expression of PI3K
in LP was significantly reduced in cardiomyocytes and in the intramural coronary
wall, while AT2R expression was unchanged in the NP group. We also found reduced
LP expression of JAK2 and STAT3. In conclusion, our data also suggest that changes
in the RAS may play a role in the ventricular growth through upregulation of the
AT1-mediated ERK1/2 response, despite unchanged AT2R expression.