Dataset Information

Effect of transverse aortic constriction on cardiac structure, function and gene expression in pregnant rats.

ABSTRACT:

Background

There is an increased risk of heart failure and pulmonary edema in pregnancies complicated by hypertensive disorders. However, in a previous study we found that pregnancy protects against fibrosis and preserves angiogenesis in a rat model of angiotensin II induced cardiac hypertrophy. In this study we test the hypothesis that pregnancy protects against negative effects of increased afterload.

Methods

Pregnant (gestational day 5.5-8.5) and non-pregnant Wistar rats were randomized to transverse aortic constriction (TAC) or sham surgery. After 14.2 ± 0.14 days echocardiography was performed. Aortic blood pressure and left ventricular (LV) pressure-volume loops were obtained using a conductance catheter. LV collagen content and cardiomyocyte circumference were measured. Myocardial gene expression was assessed by real-time polymerase chain reaction.

Results

Heart weight was increased by TAC (p<0.001) but not by pregnancy. Cardiac myocyte circumference was larger in pregnant compared to non-pregnant rats independent of TAC (p = 0.01), however TAC per se did not affect this parameter. Collagen content in LV myocardium was not affected by pregnancy or TAC. TAC increased stroke work more in pregnant rats (34.1 ± 2.4 vs 17.5 ± 2.4 mmHg/mL, p<0.001) than in non-pregnant (28.2 ± 1.7 vs 20.9 ± 1.5 mmHg/mL, p = 0.06). However, it did not lead to overt heart failure in any group. In pregnant rats, ?-MHC gene expression was reduced by TAC. Increased in the expression of ?-MHC gene was higher in pregnant (5-fold) compared to non-pregnant rats (2-fold) after TAC (p = 0.001). Nine out of the 19 genes related to cardiac remodeling were affected by pregnancy independent of TAC.

Conclusions

This study did not support the hypothesis that pregnancy is cardioprotective against the negative effects of increased afterload. Some differences in cardiac structure, function and gene expression between pregnant and non-pregnant rats following TAC indicated that afterload increase is less tolerated in pregnancy.

SUBMITTER: Songstad NT

PROVIDER: S-EPMC3930736 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Effect of transverse aortic constriction on cardiac structure, function and gene expression in pregnant rats.

Songstad Nils Thomas NT Johansen David D How Ole-Jacob OJ Kaaresen Per Ivar PI Ytrehus Kirsti K Acharya Ganesh G

PloS one 20140220 2

<h4>Background</h4>There is an increased risk of heart failure and pulmonary edema in pregnancies complicated by hypertensive disorders. However, in a previous study we found that pregnancy protects against fibrosis and preserves angiogenesis in a rat model of angiotensin II induced cardiac hypertrophy. In this study we test the hypothesis that pregnancy protects against negative effects of increased afterload.<h4>Methods</h4>Pregnant (gestational day 5.5-8.5) and non-pregnant Wistar rats were r ...[more]

PMID: 24586871

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Project description:RationaleMechanisms underlying diastolic dysfunction need to be better understood.ObjectiveTo study the role of titin in diastolic dysfunction using a mouse model of experimental heart failure induced by transverse aortic constriction.Methods and resultsEight weeks after transverse aortic constriction surgery, mice were divided into heart failure (HF) and congestive heart failure (CHF) groups. Mechanical studies on skinned left ventricle myocardium measured total and titin-based and extracellular matrix-based passive stiffness. Total passive stiffness was increased in both HF and CHF mice, and this was attributable to increases in both extracellular matrix-based and titin-based passive stiffness, with titin being dominant. Protein expression and titin exon microarray analysis revealed increased expression of the more compliant N2BA isoform at the expense of the stiff N2B isoform in HF and CHF mice. These changes are predicted to lower titin-based stiffness. Because the stiffness of titin is also sensitive to titin phosphorylation by protein kinase A and protein kinase C, back phosphorylation and Western blot assays with novel phospho-specific antibodies were performed. HF and CHF mice showed hyperphosphorylation of protein kinase A sites and the proline glutamate valine lysine (PEVK) S26 protein kinase C sites, but hypophosphorylation of the PEVK S170 protein kinase C site. Protein phosphatase I abolished differences in phosphorylation levels and normalized titin-based passive stiffness levels between control and HF myocardium.ConclusionTransverse aortic constriction-induced HF results in increased extracellular matrix-based and titin-based passive stiffness. Changes in titin splicing occur, which lower passive stiffness, but this effect is offset by hyperphosphorylation of residues in titin spring elements, particularly of PEVK S26. Thus, complex changes in titin occur that combined are a major factor in the increased passive myocardial stiffness in HF.

Dataset Information

Effect of transverse aortic constriction on cardiac structure, function and gene expression in pregnant rats.

Background

Methods

Results

Conclusions

Publications

Effect of transverse aortic constriction on cardiac structure, function and gene expression in pregnant rats.

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