Hypertrophy signaling during peripartum cardiac remodeling.
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).


CONCLUSIONS
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.
Gonzalez
A M D
AM
Department of Pediatrics, Columbia University, New York, New York, USA.
Osorio
J C
JC
Manlhiot
C
C
Gruber
D
D
Homma
S
S
Mital
S
S
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D005260:Female; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000378:metabolism*; D011270:Pregnancy, Animal / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling
D020543:Proteome