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This Article Full Text Full Text (PDF) All Versions of this Article: 293/5/H3008    most recent 00401.2007v1 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gonzalez, A. M. D. Articles by Mital, S. Search for Related Content PubMed PubMed Citation Articles by Gonzalez, A. M. D. Articles by Mital, S.

Hypertrophy signaling during peripartum cardiac remodeling

Departments of ¹Pediatrics and ²Medicine, Columbia University, New York, New York; and ³Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada

Submitted 31 March 2007 ; accepted in final form 28 August 2007

Molecular signaling pathways that regulate peripartum cardiac remodeling are not well understood. Our objectives were to study the role of mitogen-activated protein kinases (MAPKs), protein kinase B (Akt), and endothelial nitric oxide synthase (eNOS) in mediating pregnancy and postpartum (PP) cardiac remodeling. Methods: Adult female Sprague-Dawley rats were divided into nonpregnant (n = 5), 18 days pregnant (n = 5), 0 days PP (n = 7), and 14 days PP (n = 8). Rats underwent echocardiography under sedation to measure left ventricle (LV) size and function, and Western blots were performed to measure myocardial protein expression of MAPKs (p38, JNK, ERK), Akt, and eNOS. Results: 1) During pregnancy, there was an increase in LV mass (0.62 ± 0.03 to 1.1 ± 0.04 g, P < 0.001), mass/volume ratio (0.7 ± 0.02 to 1.28 ± 0.02 g/ml, P < 0.0001), and ejection fraction (EF) (64 ± 3 to 74 ± 2%). Whereas LV mass and mass/volume ratio returned to prepregnancy values in the PP period, EF remained below normal range (53 ± 3%, P < 0.05). 2) The expression of anti-hypertrophic factors (p38, JNK, Akt) decreased during pregnancy and normalized PP, except JNK, which increased to higher than normal levels. eNOS also increased to higher than baseline levels PP. 3) Activation of p38 and JNK was directly correlated with lower LV mass/volume ratio (r = –0.81 and –0.71, respectively; P < 0.05). Conclusion: Pregnancy is associated with physiological cardiac hypertrophy. There is rapid reversal of hypertrophy in the PP period while recovery of cardiac function is delayed, possibly related to PP upregulation of JNK. A dysregulation of MAPK signaling may be an important determinant of PP cardiac dysfunction.

pregnancy; cardiac hypertrophy; nitric oxide; mitogen-activated protein kinases