RAGE-mediated extracellular matrix proteins accumulation exacerbates HySu-induced pulmonary hypertension
文献类型：期刊论文
| 作者 | Jia, Daile1,2; He, Yuhu1; Zhu, Qian1,2; Liu, Huan1; Zuo, Caojian1; Lu, Ankang1; Chen, Guilin2; Yu, Ying2; , |
| 刊名 | CARDIOVASCULAR RESEARCH
 |
| 出版日期 | 2017 |
| 卷号 | 113期号:6页码:586-597 |
| 关键词 | Receptor for advanced glycation end products Pulmonary arterial smooth muscle cell Pulmonary artery Extracellular matrix proteins Pulmonary arterial hypertension |
| ISSN号 | 0008-6363 |
| DOI | 10.1093/cvr/cvx051 |
| 文献子类 | Article |
| 英文摘要 | Extracellular matrix (ECM) proteins accumulation contributes to the progression of pulmonary arterial hypertension (PAH), a rare and fatal cardiovascular condition defined by high pulmonary arterial pressure, whether primary, idiopathic, or secondary to other causes. The receptor for advanced glycation end products (RAGE) is constitutively expressed in the lungs and plays an important role in ECM deposition. Nonetheless, the mechanisms by which RAGE mediates ECM deposition/formation in pulmonary arteries and its roles in PAH progression remain unclear. Expression of RAGE and its activating ligands, S100/calgranulins and high mobility group box 1 (HMGB1), were increased in both human and mouse pulmonary arterial smooth muscle cells (PASMCs) under hypoxic conditions and were also strikingly upregulated in pulmonary arteries in hypoxia plus SU5416 (HySu)-induced PAH in mice. RAGE deletion alleviated pulmonary arterial pressure and restrained extracellular matrix accumulation in pulmonary arteries in HySu-induced PAH murine model. Moreover, blocking RAGE activity with a neutralizing antibody in human PASMCs, or RAGE deficiency in mouse PASMCs exposed to hypoxia, suppressed the expression of fibrotic proteins by reducing TGF-beta 1 expression. RAGE reconstitution in deficient mouse PASMCs restored hypoxia-stimulated TGF-beta 1 production via ERK1/2 and p38 MAPK pathway activation and subsequently increased ECM protein expression. Interestingly, HMGB1 acting on RAGE, not toll-like receptor 4 (TLR4), induced ECM deposition in PASMCs. Finally, in both idiopathic PAH patients and HySu-induced PAH mice, soluble RAGE (sRAGE) levels in serum were significantly elevated compared to those in controls. Activation of RAGE facilitates the development of hypoxia-induced pulmonary hypertension by increase of ECM deposition in pulmonary arteries. Our results indicate that sRAGE may be a potential biomarker for PAH diagnosis and disease severity, and that RAGE may be a promising target for PAH treatment. |
| 学科主题 | Cardiovascular System & Cardiology |
| WOS关键词 | GLYCATION END-PRODUCTS ; 2015 ESC/ERS GUIDELINES ; GROWTH-FACTOR-BETA ; GROUP BOX 1 ; ARTERIAL-HYPERTENSION ; VASCULAR-DISEASE ; GENE-EXPRESSION ; CHRONIC HYPOXIA ; RECEPTOR ; MANAGEMENT |
| 语种 | 英语 |
| CSCD记录号 | CSCD:31455874 |
| WOS记录号 | WOS:000400939600010 |
| 出版者 | OXFORD UNIV PRESS |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1234]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Cardiol, Sch Med, 197 Ruijiner Rd, Shanghai 200025, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab food safety Res, 320 Yueyang Rd, Shanghai 200031, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Jia, Daile,He, Yuhu,Zhu, Qian,et al. RAGE-mediated extracellular matrix proteins accumulation exacerbates HySu-induced pulmonary hypertension[J]. CARDIOVASCULAR RESEARCH,2017,113(6):586-597. |
| APA | Jia, Daile.,He, Yuhu.,Zhu, Qian.,Liu, Huan.,Zuo, Caojian.,...&,.(2017).RAGE-mediated extracellular matrix proteins accumulation exacerbates HySu-induced pulmonary hypertension.CARDIOVASCULAR RESEARCH,113(6),586-597. |
| MLA | Jia, Daile,et al."RAGE-mediated extracellular matrix proteins accumulation exacerbates HySu-induced pulmonary hypertension".CARDIOVASCULAR RESEARCH 113.6(2017):586-597. |
入库方式： OAI收割
来源：上海营养与健康研究所
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