论文库首页  论文库
 
论文编号:
论文题目: RAGE-mediated extracellular matrix proteins accumulation exacerbates HySu-induced pulmonary hypertension
英文论文题目: RAGE-mediated extracellular matrix proteins accumulation exacerbates HySu-induced pulmonary hypertension
第一作者: Jia, DL; He, YH; Zhu, Q; Liu, H; Zuo, CJ; Chen, GL; Yu, Y; Lu, AK
英文第一作者: Jia, DL; He, YH; Zhu, Q; Liu, H; Zuo, CJ; Chen, GL; Yu, Y; Lu, AK
联系作者: Lu, AK (reprint author), Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Cardiol, Sch Med, 197 Ruijiner Rd, Shanghai 200025, Peoples R China.
英文联系作者: Lu, AK (reprint author), Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Cardiol, Sch Med, 197 Ruijiner Rd, Shanghai 200025, Peoples R China.
外单位作者单位:
英文外单位作者单位:
发表年度: 2017
卷: 113
期: 6
页码: 586-597
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.
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.
刊物名称: CARDIOVASCULAR RESEARCH
英文刊物名称: CARDIOVASCULAR RESEARCH
论文全文:
英文论文全文:
全文链接:
其它备注:
英文其它备注:
学科: Cardiac & Cardiovascular Systems
英文学科: Cardiac & Cardiovascular Systems
影响因子: 5.878
第一作者所在部门:
英文第一作者所在部门:
论文出处:
英文论文出处:
论文类别: Article
英文论文类别: Article
参与作者:
英文参与作者:
 
2014 中国科学院上海生命科学研究院 版权所有