Prenatal hypoxia promotes atherosclerosis via vascular inflammation in the offspring rats.

Abstract

BACKGROUND:

Hypoxia is a critical contributor to increased risks of cardiovascular diseases, including atherosclerosis, but the detailed mechanism that hypoxia leads to atherosclerosis remains unknown.

METHODS:

Pregnant rats were treated with hypoxia (10.5% oxygen) during pregnancy, and HUVEC cells treated with 1% of oxygen. Blood lipids were tested at fetal stage and adult stage of offspring rats; the level of pro-inflammatory cytokines of HUVEC and offspring rats were investigated, and HIF-1α and NFκB mRNA level were also measured by Q-PCR and Elisa.

RESULTS:

We found that TC, LDL-C, ox-LDL-C, and the receptors of ox-LDL-C (lox-1) of the adult offspring were significantly higher than that of the control, while HDL-C was significantly reduced in hypoxia group. The internal elastic lamina was blocked by smooth muscle cells; and the migration of smooth muscle cells into the intima were observed in hypoxia offspring. Luciferase reporter gene experiment showed that HIF-1α activated NFκB transcription at four discrete binding sites of NFκBp65 promoter, although there was no obvious difference among the four discrete binding sites. Using transfection of pCDNA3.1-HIF-1α on HUVEC cells, HIF-1α significantly activated NFκB transcription at hypoxic conditions (1% O2), and concurrent with increased expression of IL-1β and TNF-α.

CONCLUSION:

Hypoxia during pregnancy activated NFκB transcription to induce pro-inflammatory cytokines, leading to the early stage of atherosclerosis.

• Authors: Pengjie Zhang, Di Zhu, Xionghui Chen, Yongmei Li, Na Li, Qinqin Gao, Lingjun Li, Xiuwen Zhou, Juanxiu Lv, Miao Sun, Caiping Mao, Zhice Xu
• Journal: Atherosclerosis (Atherosclerosis) Vol. 245 Pg. 28-34 (Feb 2016) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 26691907 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Lipids

Topics

• Animals
• Animals, Newborn
• Atherosclerosis (blood, etiology, pathology)
• Cells, Cultured
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Female
• Hypoxia (blood, complications)
• Lipids (blood)
• Pregnancy
• Pregnancy, Animal
• Rats
• Rats, Sprague-Dawley
• Vasculitis (blood, complications, pathology)