期刊
HYPERTENSION RESEARCH
卷 41, 期 2, 页码 126-134出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/hr.2017.99
关键词
human placental chorionic plate artery; large-conductance Ca2+-activated K+ channels; preeclampsia; vascular smooth muscle cells; vascular dysfunction
资金
- National Science Foundation of China [30973205, 81172464]
- National Science and Technology Pillar program of China [2014BAI05B05]
- Fundamental Research Funds for the Central Universities [2017KFYXJJ102]
Preeclampsia has known associations with insufficient placental perfusion. The large-conductance Ca2+-activated K+ (BKca) channels that have recently been found to play important roles in cellular growth and vasodilatation could potentially participate in the development of preeclampsia. However, the mechanisms by which downregulated BKca channels are involved in the development of preeclampsia remain unknown. In this study, we investigated the mechanism(s) underlying the impairment of vascular tone regulation by BKca channels in human placental chorionic plate arteries (CPAs) in preeclampsia. The levels of BKca channel alpha and beta 1 subunits were compared using immunohistochemistry, western blotting, and RT-PCR in CPAs of normal and preeclamptic pregnant women. To explore the role of BKca channels in the regulation of proliferation and apoptosis in human placental CPA smooth muscle cells (SMCs), a specific BKca opener, NS1619, was used to investigate proliferative reduction and apoptotic induction in human placental chorionic plate arterie smooth muscle cells (CPASMCs) collected from normal pregnancies. The vasodilator effects of BKca channels and their response to SNP (an NO donor) in both groups were also evaluated by wire myography. We found that BKca channel beta 1 subunits were less expressed in preeclamptic CPAs. After pretreatment with NS1619, cellular proliferation was significantly suppressed, and cellular apoptosis was dramatically promoted in cultured CPASMCs, demonstrating a relationship between increased Bax expression and decreased Bcl-2 expression in CPASMCs. Downregulated BKca is also associated with decreased vasodilatation and reduced susceptibility to NO donors. In conclusion, the decreased expression or activation of BKca channels may induce pathologic remodeling of human CPAs, weaken the vasodilation response, and decrease vascular sensitivity to vasoactive substances, thereby reducing fetal-placental blood flow and leading to the future development of preeclampsia.
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