Hypertrophy signaling during peripartum cardiac remodeling

A. M.D. Gonzalez, J. C. Osorio, Cedric Manlhiot, D. Gruber, S. Homma, S. Mital

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number5
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

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Peripartum Period
Postpartum Period
Hypertrophy
Heart Ventricles
Nitric Oxide Synthase Type III
Pregnancy
Proto-Oncogene Proteins c-akt
Mitogen-Activated Protein Kinase Kinases
Recovery of Function
Cardiomegaly
p38 Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Sprague Dawley Rats
Echocardiography
Reference Values
Up-Regulation
Western Blotting

Keywords

  • Cardiac hypertrophy
  • Mitogen-activated protein kinases
  • Nitric oxide
  • Pregnancy

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Hypertrophy signaling during peripartum cardiac remodeling. / Gonzalez, A. M.D.; Osorio, J. C.; Manlhiot, Cedric; Gruber, D.; Homma, S.; Mital, S.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 293, No. 5, 01.11.2007.

Research output: Contribution to journalArticle

Gonzalez, A. M.D. ; Osorio, J. C. ; Manlhiot, Cedric ; Gruber, D. ; Homma, S. ; Mital, S. / Hypertrophy signaling during peripartum cardiac remodeling. In: American Journal of Physiology - Heart and Circulatory Physiology. 2007 ; Vol. 293, No. 5.
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