Deng David Xing-Fei, Spin Joshua M, Tsalenko Anya, Vailaya Aditya, Ben-Dor Amir, Yakhini Zohar, Tsao Phil, Bruhn Laurakay, Quertermous Thomas
Agilent Laboratories, Palo Alto, CA, USA.
Arterioscler Thromb Vasc Biol. 2006 May;26(5):1058-65. doi: 10.1161/01.ATV.0000208185.16371.97. Epub 2006 Feb 2.
Phenotypic differences between vascular smooth muscle cell (VSMC) subtypes lead to diverse pathological processes including atherosclerosis, postangioplasty restenosis and vein graft disease. To better understand the molecular mechanisms underlying functional differences among distinct SMC subtypes, we compared gene expression profiles and functional responses to oxidized low-density lipoprotein (OxLDL) and platelet-derived growth factor (PDGF) between cultured SMCs from human coronary artery (CASM) and saphenous vein (SVSM).
OxLDL and PDGF elicited markedly different functional responses and expression profiles between the 2 SMC subtypes. In CASM, OxLDL inhibited cell proliferation and migration and modified gene expression of chemokines (CXCL10, CXCL11 and CXCL12), proinflammatory cytokines (IL-1, IL-6, and IL-18), insulin-like growth factor binding proteins (IGFBPs), and both endothelial and smooth muscle marker genes. In SVSM, OxLDL promoted proliferation partially via IGF1 signaling, activated NF-kappaB and phosphatidylinositol signaling pathways, and upregulated prostaglandin (PG) receptors and synthases. In untreated cells, alpha-chemokines, proinflammatory cytokines, and genes associated with apoptosis, inflammation, and lipid biosynthesis were higher in CASM, whereas some beta-chemokines, metalloproteinase inhibitors, and IGFBPs were higher in SVSM. Interestingly, the basal expression levels of these genes seemed closely related to their responses to OxLDL and PDGF. In summary, our results suggest dramatic differences in gene expression patterns and functional responses to OxLDL and PDGF between venous and arterial SMCs, with venous SMCs having stronger proliferative/migratory responses to stimuli but also higher expression of atheroprotective genes at baseline.
These results reveal molecular signatures that define the distinct phenotypes characteristics of coronary artery and saphenous vein SMC subtypes.
血管平滑肌细胞（VSMC）亚型之间的表型差异会导致多种病理过程，包括动脉粥样硬化、血管成形术后再狭窄和静脉移植物疾病。为了更好地理解不同平滑肌细胞亚型功能差异背后的分子机制，我们比较了来自人冠状动脉（CASM）和大隐静脉（SVSM）的培养平滑肌细胞对氧化低密度脂蛋白（OxLDL）和血小板衍生生长因子（PDGF）的基因表达谱及功能反应。
OxLDL和PDGF在这两种平滑肌细胞亚型之间引发了明显不同的功能反应和表达谱。在CASM中，OxLDL抑制细胞增殖和迁移，并改变趋化因子（CXCL10、CXCL11和CXCL12）、促炎细胞因子（IL-1、IL-6和IL-18）、胰岛素样生长因子结合蛋白（IGFBPs）以及内皮和平滑肌标记基因的表达。在SVSM中，OxLDL部分通过IGF1信号通路促进增殖，激活NF-κB和磷脂酰肌醇信号通路，并上调前列腺素（PG）受体和合成酶。在未处理的细胞中，α趋化因子、促炎细胞因子以及与凋亡、炎症和脂质生物合成相关的基因在CASM中较高，而一些β趋化因子、金属蛋白酶抑制剂和IGFBPs在SVSM中较高。有趣的是，这些基因的基础表达水平似乎与其对OxLDL和PDGF的反应密切相关。总之，我们的结果表明静脉和动脉平滑肌细胞对OxLDL和PDGF的基因表达模式和功能反应存在显著差异，静脉平滑肌细胞对刺激具有更强的增殖/迁移反应，但在基线时也具有更高的抗动脉粥样硬化基因表达。
这些结果揭示了定义冠状动脉和大隐静脉平滑肌细胞亚型不同表型特征的分子特征。
