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Marked increase in the histamine content of neointima after stent implantation of pig coronary artery and growth-promoting effects of histamine in cultured smooth muscle cells

机译:猪冠状动脉支架植入后新内膜组胺含量明显增加,组胺在培养的平滑肌细胞中具有促生长作用

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After coronary stent implantation, the unfavorable in-stent restenosis often occurs by the formation of neointima due to the proliferation of smooth muscle cells. Platelet-derived growth factor (PDGF) and other peptide growth factors contribute to this process, but little is known about the role of non-peptide factors in this process. In the present study, the role of histamine, a non-peptide factor, in the formation of neointima was investigated using a pig coronary model of in-stent restenosis and a culture system of coronary smooth muscle cells. A Palmaz-Schatz stent was implanted in the left anterior descending coronary artery of male pigs. At 1, 2 and 4 weeks after stenting, the histamine content of neointima was determined to be 326 +/- 82, 1427 +/- 280 and 440 +/- 69 pmol/mg protein, respectively, by HPLC fluorometry. In contrast, the histamine content of arterial media from the untreated control arteries was only 15.3 +/- 1.6 pmol/mg protein. These results demonstrate that the histamine content of neointima is about 20 to 90-fold that of the normal media. In vitro, histamine by itself did not stimulate the proliferation of cultured smooth muscle cells, but potentiated the PDGF-stimulated proliferation of the cultured cells via a mechanism independent of H1 and H2 histamine receptors. Thus, histamine may be an important non-peptide factor in the pathogenesis of in-stent restenosis. (c) 2005 Elsevier Inc. All rights reserved.
机译:冠状动脉支架植入后,由于平滑肌细胞的增殖,新内膜的形成常常会导致不利的支架内再狭窄。血小板衍生的生长因子(PDGF)和其他肽生长因子对此过程有贡献,但对于非肽因子在该过程中的作用知之甚少。在本研究中,使用支架内再狭窄的猪冠状动脉模型和冠状动脉平滑肌细胞培养系统,研究了非肽因子组胺在新内膜形成中的作用。将Palmaz-Schatz支架植入雄性猪的左冠状动脉前降支。在置入支架后1、2和4周,通过HPLC荧光法测定新内膜的组胺含量分别为326 +/- 82、1427 +/- 280和440 +/- 69 pmol / mg蛋白。相反,未经处理的对照动脉中动脉介质的组胺含量仅为15.3 +/- 1.6 pmol / mg蛋白。这些结果表明,新内膜的组胺含量是正常培养基的约20至90倍。在体外,组胺本身并不刺激培养的平滑肌细胞的增殖,但通过独立于H1和H2组胺受体的机制增强了PDGF刺激的培养细胞的增殖。因此,组胺可能是支架内再狭窄的发病机制中重要的非肽因子。 (c)2005 Elsevier Inc.保留所有权利。

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