Persistence of risk factors associated with maternal cardiovascular disease following aberrant inflammation in rat pregnancy.

Abstract

INTRODUCTION:

Pre-eclampsia is associated with increased risk of subsequent cardiovascular and metabolic disease in the affected mothers. While aberrant inflammation contributes to the pathophysiology of pre-eclampsia, it is unclear whether maternal inflammation contributes to the increased risk of disease. Here, we determined the effect of aberrant inflammation in pregnancy on cardiovascular and metabolic disease risk factors.

METHODS:

Wistar rats were administered low doses of lipopolysaccharide (LPS) on gestational days (GD) 13.5-16.5 to induce inflammation. Controls included pregnant rats treated with saline and nonpregnant rats treated with LPS or saline. We previously showed that LPS-treated pregnant rats exhibit key features of pre-eclampsia. Echocardiographic parameters, heart weight, blood pressure, blood lipids, pulse-wave velocity, and glucose tolerance, were assessed at 16 weeks postpartum. Messenger RNA levels of transcription factors associated with cardiac growth were measured in left ventricular tissue; histone modifications and global DNA methylation were determined in hearts and livers at GD 17.5 and at 16 weeks postpartum.

RESULTS:

Compared with saline-treated pregnant rats and nonpregnant rats treated with LPS or saline, LPS-treated pregnant rats exhibited left ventricular hypertrophy and increased blood cholesterol and low-density lipoprotein levels at 16 weeks postdelivery. LPS-treated rats had increased left ventricular mRNA levels of hypertrophy-associated transcription factors at GD 17.5 and increased levels of modified histones in hearts and livers at GD 17.5 and 16 weeks postpartum. Other parameters remained unchanged.

CONCLUSION:

Aberrant inflammation during pregnancy results in persistent alterations in maternal physiological parameters and epigenetic modifications that could contribute to the pathophysiology of cardiovascular disease.

• Authors: Takafumi Ushida, Shannyn K Macdonald-Goodfellow, Allegra Quadri, M Yat Tse, Louise M Winn, Stephen C Pang, Michael A Adams, Tomomi Kotani, Fumitaka Kikkawa, Charles H Graham
• Journal: Biology of reproduction (Biol Reprod) Vol. 97 Issue 1 Pg. 143-152 (Jul 01 2017) ISSN: 1529-7268 [Electronic] United States
• PMID: 28859286 (Publication Type: Journal Article)
• Copyright: © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: [email protected]

Chemical References

• Histones
• Lipopolysaccharides
• DNA

Topics

• Animals
• Blood Pressure
• DNA (genetics, metabolism)
• Echocardiography
• Female
• Gene Expression Regulation
• Heart
• Histones (genetics, metabolism)
• Inflammation (chemically induced, complications)
• Lipopolysaccharides (toxicity)
• Pregnancy
• Pregnancy Complications, Cardiovascular
• Rats
• Rats, Wistar
• Risk Factors