Prenatal hypoxia promotes atherosclerosis via vascular inflammation in the offspring rats. (February 2016)

• Record Type: Journal Article
• Authors: Zhang, Pengjie; Zhu, Di; Chen, Xionghui; Li, Yongmei; Li, Na; Gao, Qinqin; Li, Lingjun; Zhou, Xiuwen; Lv, Juanxiu; Sun, Miao; Mao, Caiping; Xu, Zhice
• Is Part Of: Atherosclerosis. Volume 245(2016)
• Page Start: 28
• Page End: 34
• Publication Date: 2016-02
• Subjects: Prenatal hypoxia -- Atherosclerosis -- Inflammation -- Pro-inflammatory cytokines; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.11.028
• Languages: English
• ISSNs: 0021-9150

Abstract

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. Graphical abstract: Highlights: Early stage of atherosclerosis was found in maternal hypoxia group, not CON group. Atherosclerosis formation was caused by inflammation in offspring rats. The activity among four HIF-1α binding sites in NFκBp65 promoter was equivalent.