Pericardial interstitial cell senescence responsible for pericardial structural remodeling in idiopathic and postsurgical constrictive pericarditis
Pericardial interstitial cell senescence responsible for pericardial structural remodeling in idiopathic and postsurgical constrictive pericarditis
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DOI：
10.1016/j.jtcvs.2017.03.115
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发表时间：
2017-09
期刊：
影响因子：
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通讯作者：
Lin Han;Xin Li;Guan‐xin Zhang;Zhiyun Xu;De-jun Gong;F. Lu;Xiaohong Liu
中科院分区：
文献类型：
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作者：
Lin Han;Xin Li;Guan‐xin Zhang;Zhiyun Xu;De-jun Gong;F. Lu;Xiaohong Liu
目的特发性和术后缩窄性心包炎以心包结构重构为特征，包括纤维化、钙化和炎症。本研究旨在确定细胞衰老是否与心包结构重塑有关。方法采集特发性或术后心包炎患者的心包间质细胞（心包炎细胞）。在年龄和性别匹配的对照组（非心包炎细胞）之间比较衰老时间和端粒长度的差异。从正常心包中提取的心包间质细胞依次传代至衰老（衰老细胞）。比较衰老细胞与传代2的非衰老细胞（非衰老细胞）的凋亡、胶原基质、钙沉积、化学引诱物特性、基因表达谱和旁分泌效应。结果心包炎细胞呈现衰老变化，端粒长度短，细胞大小扁平，衰老相关β-半乳糖苷酶染色阳性，生长能力受限。与非衰老细胞相比，这些衰老细胞具有抗凋亡能力，产生更多的胶原基质，沉积更多的钙，吸引更多的单核细胞/淋巴细胞。参与细胞外基质沉积（结缔组织生长因子、纤维连接蛋白、I型胶原、III型胶原和金属蛋白酶-1的组织抑制剂）、钙沉积（骨桥蛋白、骨唾液蛋白、骨连接蛋白和基质Gla蛋白）和炎症细胞募集（白细胞介素-6、趋化蛋白-1和肿瘤坏死因子-α）的基因簇在衰老细胞中上调。细胞外基质降解酶（金属蛋白酶-1和金属蛋白酶-3）表达下调。此外，衰老细胞具有促进邻近细胞增殖、分化和衰老的能力。结论衰老细胞具有促进心包结构重塑的特点，但其原因尚需进一步研究。
ObjectiveIdiopathic and postsurgical constrictive pericarditis is characterized by pericardial structural remodeling that involves fibrosis, calcification, and inflammation. This study aimed to determine whether cell senescence was responsible for pericardial structural remodeling.MethodsPericardial interstitial cells derived from patients with idiopathic or postsurgical pericarditis (pericarditis cells) were harvested. Timing of senescence and differences in telomere length were compared between age- and sex-matched controls (nonpericarditis cells). Pericardial interstitial cells derived from normal pericardia were serially passaged until senescence (senescent cells). Apoptosis, collagen matrix, calcium deposition, chemoattractant properties, gene expression profiles, and paracrine effects of senescent cells were compared with nonsenescent cells of passage 2 (nonsenescent cells).ResultsPericarditis cells displayed senescent changes, including short telomere length, large flattened cell sizes, positive staining for senescence-associated β-galactosidase, and limited growth capacity. These senescent cells were resistant to apoptosis, produced more collagen matrix, deposited more calcium, and attracted more monocytes/lymphocytes than the nonsenescent cells. A cluster of genes involved in extracellular matrix deposition (connective tissue growth factor, fibronectin, collagen type I, collagen type III, and tissue inhibitors of metalloproteinase-1), calcium deposition (osteopontin, bone sialoprotein, osteonectin, and matrix Gla protein), and inflammatory cell recruitment (interleukin-6, chemoattractant protein-1, and tumor necrosis factor-α) were upregulated in senescent cells, whereas extracellular matrix-degrading enzyme (metalloproteinase-1 and metalloproteinase-3) was downregulated. Furthermore, senescent cells had the ability to promote the proliferation, differentiation, and senescence of neighboring cells.ConclusionsThese findings suggest that senescent cells have characteristics promoting pericardial structural remodeling, but further work is needed to establish causation.