RAT CAROTID NEOINTIMAL SMOOTH-MUSCLE CELLS REEXPRESS A DEVELOPMENTALLY REGULATED MESSENGER-RNA PHENOTYPE DURING REPAIR OF ARTERIAL INJURY
RAT CAROTID NEOINTIMAL SMOOTH-MUSCLE CELLS REEXPRESS A DEVELOPMENTALLY REGULATED MESSENGER-RNA PHENOTYPE DURING REPAIR OF ARTERIAL INJURY
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DOI：
10.1161/01.res.71.4.759
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发表时间：
1992-10-01
影响因子：
20.1
通讯作者：
SCHWARTZ, SM
中科院分区：
文献类型：
--
作者：
MAJESKY, MW;GIACHELLI, CM;SCHWARTZ, SM
从损伤的大鼠颈动脉新生内膜培养的平滑肌细胞（SMC）在体外具有与来自未损伤的中膜的SMC不同的形状和组织。来自成年大鼠的新生内膜SMC的形态非常类似于来自12日龄大鼠幼仔的中膜SMC的子集。在本研究中，我们发现成人颈动脉新生内膜SMC在体外表达血小板衍生生长因子（PDGF）-B基因，但很少或没有PDGF α受体mRNA。相反，在相同条件下生长和传代的对侧未损伤颈动脉的中膜SMC含有丰富的PDGF α受体mRNA，但很少或没有PDGF-B mRNA。PDGF-A或PDGF β受体的转录水平在新生内膜与中膜SMC培养物中没有差异。成年新生内膜SMC的PDGF mRNA表型与新生大鼠幼仔主动脉中膜SMC亚群非常相似。虽然有趣，我们在细胞培养中观察到的SMC表型的差异可能取决于体外的独特条件，并不一定意味着类似的SMC多样性也存在于体内。为了解决这个问题，我们构建并筛选了一个SMC cDNA文库，以寻找常见的“蛹-内膜”SMC表型的其他分子标记。两个cDNA克隆，其同源mRNA水平在大鼠主动脉在体内发育调节，并在高水平的成人颈动脉新生内膜形成后2周球囊导管损伤。重要的是，在体外培养的新生内膜与中膜SMC中，颈动脉新生内膜中这两种同源mRNA的水平高于下层中膜。DNA序列分析表明，cDNA克隆编码大鼠弹性蛋白原和α-1前胶原（I型）。这些结果提供了进一步的证据表明，在成年大鼠颈动脉新生内膜的形成取决于SMC表型或亚群的再表达与动脉壁发育的早期阶段的特殊属性的特点。我们迄今的研究表明，这些特殊性质中的两个是旁分泌生长因子的产生和细胞外基质的合成。
Smooth muscle cells (SMCs) cultured from the neointima of injured rat carotid arteries have a different shape and organization in vitro than SMCs from the uninjured media. The morphology of neointimal SMCs from adult rats strongly resembles that of a subset of medial SMCs from 12-day-old rat pups. In the present study, we show that adult carotid neointimal SMCs in vitro express the platelet-derived growth factor (PDGF)-B gene but have little or no PDGF alpha-receptor mRNA. In contrast, medial SMCs from contralateral uninjured carotids, grown and passaged under identical conditions, contain abundant PDGF alpha-receptor mRNA but little or no PDGF-B mRNA. Transcript levels for PDGF-A or PDGF beta-receptor were not different in neointimal versus medial SMC cultures. The PDGF mRNA phenotype of adult neointimal SMCs strongly resembles that of an aortic medial SMC subset from newborn rat pups. Although intriguing, the differences in SMC phenotypes we observed in cell culture may depend on unique conditions in vitro and do not necessarily mean that analogous SMC diversity also exists in vivo. To address this question, we constructed and screened a SMC cDNA library for additional molecular markers of the common "pup-intimal" SMC phenotype. Two cDNA clones were identified whose cognate mRNA levels were developmentally regulated in rat aorta in vivo and were present at high levels in the adult carotid neointima formed 2 weeks after balloon catheter injury. Importantly, elevated levels of these two cognate mRNAs in carotid neointima compared with underlying media were maintained in cultures of neointimal versus medial SMCs in vitro. DNA sequence analysis indicated that the cDNA clones encoded rat tropoelastin and alpha-1 procollagen (type I). These results provide further evidence that neointima formation in the adult rat carotid artery depends on reexpression of an SMC phenotype or subpopulation with special properties characteristic of earlier stages of artery wall development. Our studies to date indicate that two of these special properties are paracrine growth factor production and extracellular matrix synthesis.