血管舒张
血管收缩
医学
钙
内体
内科学
血流动力学
缺氧性肺血管收缩
心脏病学
生物学中的钙
药理学
肺
内皮
肺动脉高压
呼吸系统
细胞
内分泌学
血管阻力
血管疾病
疾病
肺动脉
作者
Jason H. Karnes,Changlei Bao,Shuxin Liang,Timothy Thayer,John Zagorski,Samisubbu R. Naidu,James D. West,Tae-Hwi Schwantes-An,Ehsan Khajouei,Kasturi Banerjee,Hemant K. Tiwari,Juvie Farol,Kiana L. Martinez,D Q Liu,Ning Yao,Yanan Sun,Yangfan Jia,Jian Wang,Amit Arora,Ken Batai
出处
期刊:Circulation Research
[Lippincott Williams & Wilkins]
日期:2026-05-18
卷期号:139 (2): e327117-e327117
被引量:1
标识
DOI:10.1161/circresaha.125.327117
摘要
BACKGROUND: Although pulmonary arterial hypertension (PAH) is a rare and fatal disease that is well-characterized, vasodilator-responsive PAH accounts for a minority of cases, with little mechanistic knowledge, but with dramatically improved survival. METHODS: By assembling national cohorts, we evaluated genetic influences on acute vasodilator drug response, a key determinant of the presence of vasodilator-responsive PAH. Differences between hemodynamics at rest and after a PAH-specific vasodilator were tested in a genome-wide association study. Validated loci were functionally tested in cell culture and in a hypoxic mouse model of pulmonary hypertension. RESULTS: =0.027). Consistent with its predicted function, SNX29 demonstrated an endosomal distribution in PA smooth muscle cells. Silencing SNX29 redistributed stromal interaction molecule proteins to the cell membrane and enhanced store-operated calcium entry. Over-expression of SNX29, in vivo, attenuated hypoxic vasoconstriction in isolated perfused murine lung models. CONCLUSIONS: The data cumulatively suggest SNX29 may contribute to vasodilation partly through reduced store-operated calcium entry and endosomal trafficking of store-operated calcium entry proteins, advancing our understanding of vasodilator-responsive PAH.
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