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Pressure overload induces greater hypertrophy and mortality in female mice with p38alpha MAPK inhibition.

Publication ,  Journal Article
Liu, J; Sadoshima, J; Zhai, P; Hong, C; Yang, G; Chen, W; Yan, L; Wang, Y; Vatner, SF; Vatner, DE
Published in: J Mol Cell Cardiol
October 2006

We examined pressure overload left ventricular (LV) hypertrophy (H) induced by aortic banding in transgenic mice with cardiac-specific expression of a dominant negative (DN) p38alpha (TG) and wild type controls (WT). In response to chronic pressure overload, induced by aortic constriction, LV/BW increased more, p<0.05, in female TG (6.4+/-0.2, n=7) than in WT female (5.1+/-0.2, n=10), or male TG or WT (5.0+/-0.2, n=10 vs. 5.5+/-0.2, n=8). Lung/BW, an index of LV decompensation, was significantly higher, p<0.05, in banded female TG (14+/-1.2 mg/g) than in WT females (9.0+/-0.8), or male TG or WT (8.2+/-0.7 vs. 9.3+/-1.3). This was associated with higher premature mortality, p<0.05, in banded female TG mice (42%) compared with banded WT females (10%), TG males (13%), or WT males (17%). In male, but not female, TG mice, the number of TUNEL-positive cells was smaller, p<0.05, compared with WT. Phospho-Akt kinase activity increased (p<0.05) in female TG after banding, but not in males. After ovariectomy, chronic pressure overload no longer induced greater mortality, greater LVH, or p-Akt levels in female TG mice, and like male TG mice, apoptosis was protected. DN-p38alpha enhanced estrogen-induced activation of Akt in cultured cardiac myocytes. Thus, inhibition of p38alpha MAPK paradoxically augments LVH resulting in cardiac decompensation and increased mortality in response to pressure overload more in female mice than male mice, which could be due to increased Akt activation and/or through cross-talk between p38alpha MAPK and Akt.

Duke Scholars

Published In

J Mol Cell Cardiol

DOI

ISSN

0022-2828

Publication Date

October 2006

Volume

41

Issue

4

Start / End Page

680 / 688

Location

England

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Ventricular Pressure
  • Sex Factors
  • Rats, Wistar
  • Rats
  • Proto-Oncogene Proteins c-akt
  • Phosphorylation
  • Ovariectomy
  • Mice, Transgenic
  • Mice
 

Citation

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Liu, J., Sadoshima, J., Zhai, P., Hong, C., Yang, G., Chen, W., … Vatner, D. E. (2006). Pressure overload induces greater hypertrophy and mortality in female mice with p38alpha MAPK inhibition. J Mol Cell Cardiol, 41(4), 680–688. https://doi.org/10.1016/j.yjmcc.2006.07.007
Liu, Jing, Junichi Sadoshima, Peiyong Zhai, Chull Hong, Guiping Yang, Wei Chen, Lin Yan, Yibin Wang, Stephen F. Vatner, and Dorothy E. Vatner. “Pressure overload induces greater hypertrophy and mortality in female mice with p38alpha MAPK inhibition.J Mol Cell Cardiol 41, no. 4 (October 2006): 680–88. https://doi.org/10.1016/j.yjmcc.2006.07.007.
Liu J, Sadoshima J, Zhai P, Hong C, Yang G, Chen W, et al. Pressure overload induces greater hypertrophy and mortality in female mice with p38alpha MAPK inhibition. J Mol Cell Cardiol. 2006 Oct;41(4):680–8.
Liu, Jing, et al. “Pressure overload induces greater hypertrophy and mortality in female mice with p38alpha MAPK inhibition.J Mol Cell Cardiol, vol. 41, no. 4, Oct. 2006, pp. 680–88. Pubmed, doi:10.1016/j.yjmcc.2006.07.007.
Liu J, Sadoshima J, Zhai P, Hong C, Yang G, Chen W, Yan L, Wang Y, Vatner SF, Vatner DE. Pressure overload induces greater hypertrophy and mortality in female mice with p38alpha MAPK inhibition. J Mol Cell Cardiol. 2006 Oct;41(4):680–688.
Journal cover image

Published In

J Mol Cell Cardiol

DOI

ISSN

0022-2828

Publication Date

October 2006

Volume

41

Issue

4

Start / End Page

680 / 688

Location

England

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Ventricular Pressure
  • Sex Factors
  • Rats, Wistar
  • Rats
  • Proto-Oncogene Proteins c-akt
  • Phosphorylation
  • Ovariectomy
  • Mice, Transgenic
  • Mice