ty -jour t1-针对特发性肺动脉高压抗体和重塑的靶向TMEM16A逆转血管收缩和重塑JF-欧洲呼吸杂志Nagaraj, Chandran AU - Zabini, Diana AU - Nagy, Bence M. AU - Lengyel, Miklós AU - Skofic Maurer, Davor AU - Sharma, Neha AU - Egemnazarov, Bakytbek AU - Kovacs, Gabor AU - Kwapiszewska, Grazyna AU - Marsh,Leigh M. AU - Hrzenjak, Andelko AU - Höfler, Gerald AU - Didiasova, Miroslava AU - Wygrecka, Malgorzata AU - Sievers, Laura K. AU - Szucs, Peter AU - Enyedi, Péter AU - Ghanim, Bahil AU - Klepetko, WalterAu -Olschewski，Horst au -Olschewski，Andrea Y1-2019/06/01 Ur -http：//www.qdcxjkg.com/content.com/content/53/6/1800965.ABSTRART肺动脉高压（IPAH）显示Cl-通道TMEM16A基因的上调。我们假设TMEM16A的过表达可能代表了引起肺动脉高压的分子途径中的新型恶性循环（PAH）。我们研究了健康的供体肺（n = 40）和带有IPAH的受体肺（n = 38），用于表达阴离子通道和阴离子通道和表达。小型肺动脉和肺动脉平滑肌细胞中的转运蛋白基因（PASMC）。在IPAH中，TMEM16A强烈上调，斑块钳记录证实了PASMC中的Cl-电流增加（n = 9-10）。这些细胞被去极化，可以通过TMEM16A抑制剂或敲低实验（n = 6-10）复制。TMEM16A的抑制/敲除可以减少IPAH-PASMC的增殖（n = 6）。相反，健康供体PASMC中TMEM16A的过表达产生了类似IPAH的表型。 Chronic application of benzbromarone in two independent animal models significantly decreased right ventricular pressure and reversed remodelling of established pulmonary hypertension.Our findings suggest that increased TMEM16A expression and activity comprise an important pathologic mechanism underlying the vasoconstriction and remodelling of pulmonary arteries in PAH. Inhibition of TMEM16A represents a novel therapeutic approach to reverse remodelling in PAH.TMEM16A plays a central role in the pathological mechanisms underlying the depolarisation, vasoconstriction and proliferation of PASMCs, contributing to the increased pulmonary vascular resistance in PAH, thus providing a novel target for PAH therapy http://ow.ly/3Rs330o3CUy ER -