Novel effects of adenosine receptors on pericellular hyaluronan matrix: implications for human smooth muscle cell phenotype and interactions with monocytes during atherosclerosis
Novel effects of adenosine receptors on pericellular hyaluronan matrix: implications for human smooth muscle cell phenotype and interactions with monocytes during atherosclerosis
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腺苷受体对细胞周围透明质酸基质的新作用：对人平滑肌细胞表型以及动脉粥样硬化期间与单核细胞相互作用的影响
DOI：
10.1007/s00395-013-0340-6
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发表时间：
2013
影响因子：
9.5
通讯作者：
Fischer JW
中科院分区：
文献类型：
--
作者：
Grandoch M;Hoffmann J;Rock K;Wenzel F;Oberhuber A;Schelzig H;Fischer JW
透明质酸（HA）对促动脉粥样硬化生长因子和细胞因子有反应，并被认为有助于新生内膜增生和动脉粥样硬化。然而，细胞周HA基质的特定功能可能取决于相应的刺激。腺苷在血管平滑肌细胞（VSMC）的表型调节中起重要作用，并被认为可抑制动脉粥样硬化过程中的炎症反应。本研究的目的是研究腺苷对人冠状动脉平滑肌细胞（HCASMC）HA基质的调节和功能。腺苷受体激动剂NECA（10 μM）在6 h时引起HA合成酶（HAS）1的强烈诱导，24 h后再次引起较弱的诱导。选择性腺苷受体拮抗剂的使用表明，腺苷A2 B受体（A2 BR）介导早期HAS 1诱导，而晚期HAS 1诱导通过A2 AR和A3 R介导。6 h后的强烈反应部分通过磷酸肌醇-3激酶和促分裂原活化蛋白激酶途径介导，并被Epac抑制。在功能上，NECA增加了细胞迁移，这被shRNA介导的HAS 1敲低所消除。除了HA分泌外，NECA还刺激HCASMC中明显的细胞周HA基质的形成，并增加单核细胞的粘附。腺苷诱导的单核细胞粘附对透明质酸酶敏感。总之，目前的数据表明，腺苷通过腺苷A2 BR和A2 AR/A3 R诱导HAS 1。反过来，HCASMC形成富含HA的基质，其可能支持迁移性HCASMC表型并将单核细胞/巨噬细胞捕获在间质基质中。
Hyaluronan (HA) is responsive to pro-atherosclerotic growth factors and cytokines and is thought to contribute to neointimal hyperplasia and atherosclerosis. However, the specific function of the pericellular HA matrix is likely depend on the respective stimuli. Adenosine plays an important role in the phenotypic regulation of vascular smooth muscle cells (VSMC) and is thought to inhibit inflammatory responses during atherosclerosis. The aim of this study was to examine the regulation and function of HA matrix in response to adenosine in human coronary artery SMC (HCASMC). The adenosine receptor agonist NECA (10 μM) caused a strong induction of HA synthase (HAS)1 at 6 h and a weaker induction again after 24 h. Use of selective adenosine receptor antagonists revealed that adenosine A2Breceptors (A2BR) mediate the early HAS1 induction, whereas late HAS1 induction was mediated via A2AR and A3R. The strong response after 6 h was mediated in part via phosphoinositide-3 kinase- and mitogen-activated protein kinase pathways and was inhibited by Epac. Functionally, NECA increased cell migration, which was abolished by shRNA-mediated knock down of HAS1. In addition to HA secretion, NECA also stimulated the formation of pronounced pericellular HA matrix in HCASMC and increased the adhesion of monocytes. The adenosine-induced monocyte adhesion was sensitive to hyaluronidase. In conclusion, the current data suggest that adenosine via adenosine A2BR and A2AR/A3R induces HAS1. In turn a HA-rich matrix is formed by HCASMC which likely supports the migratory HCASMC phenotype and traps monocytes/macrophages in the interstitial matrix.
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影响因子：
29.4
作者：
Odashima, M;Bamias, G;Cominelli, F
通讯作者：
Cominelli, F
影响因子：
8.3
作者：
Dubey, RK;Gillespie, DG;Jackson, EK
通讯作者：
Jackson, EK
影响因子：
15.9
作者：
Yang, Dan;Zhang, Ying;Ravid, Katya
通讯作者：
Ravid, Katya
DOI：
10.1152/ajpheart.00741.2001
发表时间：
2002-03-01
影响因子：
4.8
作者：
Yang, ZQ;Cerniway, RJ;Matherne, GP
通讯作者：
Matherne, GP
DOI：
10.1161/atvbaha.109.188839
发表时间：
2009-07
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Wang H;Zhang W;Zhu C;Bucher C;Blazar BR;Zhang C;Chen JF;Linden J;Wu C;Huo Y
通讯作者：
Huo Y