Endothelial Cell-Derived SO(2) Controls Endothelial Cell Inflammation, Smooth Muscle Cell Proliferation, and Collagen Synthesis to Inhibit Hypoxic Pulmonary Vascular Remodelling.
Endothelial Cell-Derived SO(2) Controls Endothelial Cell Inflammation, Smooth Muscle Cell Proliferation, and Collagen Synthesis to Inhibit Hypoxic Pulmonary Vascular Remodelling.
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内皮细胞衍生的SO（2）控制内皮细胞炎症，平滑肌细胞增殖和胶原蛋白合成以抑制缺氧性肺血管重塑。
DOI：
10.1155/2021/5577634
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发表时间：
2021
影响因子：
--
通讯作者：
Jin H
中科院分区：
文献类型：
--
作者：
Liu X;Zhang S;Wang X;Wang Y;Song J;Sun C;Chen G;Yang G;Tao Y;Hu Y;Bu D;Huang Y;Du J;Jin H
缺氧性肺血管重构(PVR)是老年慢性阻塞性肺疾病和阻塞性睡眠呼吸暂停综合征的主要病理基础。肺动脉内皮细胞(PAEC)炎症、肺动脉平滑肌细胞(PASMC)增殖、肥大和胶原重构是PVR的重要病理生理成分。内源性二氧化硫(SO2)是一种新型的心血管系统气体递质，具有独特的生物学特性。本研究旨在探讨内皮细胞来源的SO2在PVR的PAEC炎症、PASMC增殖、肥大和胶原重塑中的作用及其可能的机制。建立EC特异性天冬氨酸氨基转移酶1转基因小鼠(EC-AAT1-TG)。低氧诱导大鼠肺动脉高压。采用右心导管法和超声心动图检测小鼠血流动力学变化。取肺动脉进行病理分析。采用高效液相色谱检测二氧化硫含量。将含AAT1cDNA或shRNA慢病毒的人肺内皮细胞(HPAECs)与共培养的人PASMCs(HPASMCs)共培养。采用SO2探针法和酶联免疫吸附试验分别检测SO2含量和p50活性。低氧可显著降低小鼠肺和HPAECs中SO2含量，增加右室收缩压、肺动脉壁厚度、肌化程度和PAECICAM-1、MCP-1、PASMC Ki-67、I型胶原和α-SMA的表达(p<；0.05)。然而，充足SO2含量的EC-AAT1-TG可抑制缺氧引起的上述升高(p<；0.05)。在机制上，EC来源的SO2缺乏促进HPAEC ICAM-1和MCP-1以及共同培养的HPASMC Ki-67和I型胶原的表达，这一作用可被p50的抑制剂穿心莲内酯阻断(p<；0.05)。同时，EC来源的二氧化硫缺乏增加了共同培养的HPASMCα-SMA的表达(p<；0.05)。综上所述，这些结果表明，EC来源的SO2以自分泌方式抑制p50的激活，以自分泌方式抑制PAEC炎症，以旁分泌方式抑制PASMC的增殖、肥大和胶原合成，从而抑制缺氧性PVR。
Hypoxic pulmonary vascular remodelling (PVR) is the major pathological basis of aging-related chronic obstructive pulmonary disease and obstructive sleep apnea syndrome. The pulmonary artery endothelial cell (PAEC) inflammation, and pulmonary artery smooth muscle cell (PASMC) proliferation, hypertrophy and collagen remodelling are the important pathophysiological components of PVR. Endogenous sulfur dioxide (SO2) was found to be a novel gasotransmitter in the cardiovascular system with its unique biological properties. The study was aimed to investigate the role of endothelial cell- (EC-) derived SO2 in the progression of PAEC inflammation, PASMC proliferation, hypertrophy and collagen remodelling in PVR and the possible mechanisms. EC-specific aspartic aminotransferase 1 transgenic (EC-AAT1-Tg) mice were constructed in vivo. Pulmonary hypertension was induced by hypoxia. Right heart catheterization and echocardiography were used to detect mouse hemodynamic changes. Pathologic analysis was performed in the pulmonary arteries. High-performance liquid chromatography was employed to detect the SO2 content. Human PAECs (HPAECs) with lentiviruses containing AAT1 cDNA or shRNA and cocultured human PASMCs (HPASMCs) were applied in vitro. SO2 probe and enzyme-linked immunosorbent assay were used to detect the SO2 content and determine p50 activity, respectively. Hypoxia caused a significant reduction in SO2 content in the mouse lung and HPAECs and increases in right ventricular systolic pressure, pulmonary artery wall thickness, muscularization, and the expression of PAEC ICAM-1 and MCP-1 and of PASMC Ki-67, collagen I, and α-SMA (p < 0.05). However, EC-AAT1-Tg with sufficient SO2 content prevented the above increases induced by hypoxia (p < 0.05). Mechanistically, EC-derived SO2 deficiency promoted HPAEC ICAM-1 and MCP-1 and the cocultured HPASMC Ki-67 and collagen I expression, which was abolished by andrographolide, an inhibitor of p50 (p < 0.05). Meanwhile, EC-derived SO2 deficiency increased the expression of cocultured HPASMC α-SMA (p < 0.05). Taken together, these findings revealed that EC-derived SO2 inhibited p50 activation to control PAEC inflammation in an autocrine manner and PASMC proliferation, hypertrophy, and collagen synthesis in a paracrine manner, thereby inhibiting hypoxic PVR.
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影响因子：
3.9
作者：
Piera-Velazquez S;Mendoza FA;Jimenez SA
通讯作者：
Jimenez SA
DOI：
10.1161/hypertensionaha.118.10865
发表时间：
2018-05
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
De Silva TM;Modrick ML;Dabertrand F;Faraci FM
通讯作者：
Faraci FM
影响因子：
20.1
作者：
North BJ;Sinclair DA
通讯作者：
Sinclair DA
H2S 抑制野百合碱诱导的肺动脉高压大鼠肺动脉内皮细胞炎症
影响因子：
5
作者：
Feng, Shasha;Chen, Siyao;Jin, Hongfang
通讯作者：
Jin, Hongfang
影响因子：
--
作者：
Blaha, Igor;Elvira Lopez-Oliva, Maria;Hernandez, Medardo
通讯作者：
Hernandez, Medardo