Sodium Tanshinone IIA Sulfonate Inhibits Canonical Transient Receptor Potential Expression in Pulmonary Arterial Smooth Muscle from Pulmonary Hypertensive Rats

被引：92

作者：

Wang, Jian ^{[1
,2
]}

Jiang, Qian ^{[1
]}

Wan, Limei ^{[1
]}

Yang, Kai ^{[1
,2
]}

Zhang, Yi ^{[1
,2
]}

Chen, Yuqin ^{[1
]}

Wang, Elizabeth ^{[3
]}

Lai, Ning ^{[1
,2
]}

Zhao, Lei ^{[1
]}

Jiang, Hua ^{[1
]}

Sun, Yueqian ^{[4
]}

Zhong, Nanshan ^{[1
]}

Ran, Pixin ^{[1
]}

Lu, Wenju ^{[1
]}

机构：

[1] Guangzhou Med Univ, Affiliated Hosp 1, State Key Lab Resp Dis, Guangzhou Inst Resp Dis, Guangzhou 510120, Guangdong, Peoples R China

[2] Johns Hopkins Med Inst, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA

[3] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA

[4] Univ Toronto, Dept Arts & Sci, Toronto, ON, Canada

来源：

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY | 2013年 / 48卷 / 01期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

STS; TRPC; SOCE; pulmonary hypertension; OPERATED CA2+ ENTRY; COMBINATION THERAPY; INTRACELLULAR CA2+; GENE-EXPRESSION; TRPC EXPRESSION; ACUTE-HYPOXIA; A SULFONATE; CHANNELS; PROTEIN; RESPONSES;

D O I：

10.1165/rcmb.2012-0071OC

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Danshen, the dried root of Salvia miltiorrhiza, is widely used in clinics in China for treating various diseases, including cardiovascular diseases. Sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA isolated as the major active component from Danshen, was recently reported to be effective in attenuating the characteristic pulmonary vascular changes associated with chronically hypoxic pulmonary hypertension (CHPH); however, the underlying detailed mechanisms are poorly understood. In this study, we investigated the effects of STS on basal intracellular Ca2+ concentration ([Ca2+](i)) and store-operated Ca2+ entry (SOCE) in distal pulmonary arterial smooth muscle cells (PASMCs) exposed to prolonged hypoxia or isolated from CHPH rats. SOCE measured by Mn2+ quenching of Fura-2 fluorescence in PASMCs from rats exposed to chronic hypoxia (10% O-2, 21 d) was increased by 59%, and basal [Ca2+](i) was increased by 119%; this effect was inhibited by intraperitoneal injection of STS. These inhibitory effects of STS on hypoxic increases of SOCE and basal [Ca2+](i) were associated with reduced expression of canonical transient receptor potential (TRPC) 1 and TRPC6 in distal pulmonary arterial smooth muscle and decreases on right ventricular pressure, right ventricular hypertrophy, and peripheral pulmonary vessel thickening. In ex vivo cultured distal PASMCs from normoxic rats, STS (0-25 mu M) dose-dependently inhibited hypoxia induced cell proliferation and migration, paralleled with attenuation in increases of basal [Ca2+](i), SOCE, mRNA, and protein expression of TRPC1 and TRPC6. STS also relieved right ventricular systolic pressure, right ventricular hypertrophy, and TRPC1 and TRPC6 protein expression in distal pulmonary arteries in a monocrotaline-induced rat model of pulmonary arterial hypertension. These results indicate that STS prevents pulmonary arterial hypertension development likely by inhibiting TRPC1 and TRPC6 expression, resulting in normalized basal [Ca2+](i) and attenuated proliferation and migration of PASMCs.

引用

页码：125 / 134

页数：10

共 61 条

[1]

Role of Combination Therapy in the Treatment of Pulmonary Arterial Hypertension [J].