Stress and vascular responses: anti-inflammatory therapeutic strategy against atherosclerosis and restenosis after coronary intervention.
Stress and vascular responses: anti-inflammatory therapeutic strategy against atherosclerosis and restenosis after coronary intervention.
复制标题
DOI：
10.1254/jphs.91.192
复制
发表时间：
2003
影响因子：
3.5
通讯作者：
S. Kitamoto;K. Egashira;A. Takeshita
中科院分区：
文献类型：
--
作者：
S. Kitamoto;K. Egashira;A. Takeshita
经皮冠状动脉介入治疗后的动脉粥样硬化和再狭窄已成为西方国家公共卫生的主要问题。近年来的研究表明，炎症在心血管疾病的发病机制中起着重要作用。血管损伤可能涉及炎症反应，其通过单核细胞趋化蛋白-1（MCP-1）加速单核细胞的募集和活化。MCP-1的表达在动脉粥样硬化病变和球囊损伤的动脉中增加。最近，我们设计了一种新的抗MCP-1基因治疗策略，即将突变MCP-1基因转染到骨骼肌中。这种突变型MCP-1已显示作为MCP-1的显性负性抑制剂起作用。我们在这里证明，这种策略限制了预先存在的动脉粥样硬化病变的进展，并改善了高胆固醇血症小鼠的病变组成，使其成为更稳定的表型。该策略还抑制了损伤部位的单核细胞浸润/活化，并显著抑制了球囊损伤或支架植入后兔、大鼠和猴颈动脉的再狭窄变化（新生内膜增生）。因此，MCP-1介导的单核细胞浸润在再狭窄变化和动脉粥样硬化进展中是必不可少的。MCP-1可能成为治疗动脉粥样硬化和再狭窄的一个有效靶点。
Atherosclerosis and restenosis after percutaneous coronary interventions have become major issues in public health in Western countries. Recent studies have revealed that inflammation plays an important role in pathogenesis of cardiovascular diseases. Vascular injury may involve an inflammatory response, which accelerates the recruitment and activation of monocytes through monocyte chemoattractant protein-1 (MCP-1). MCP-1 expression has been shown to be increased in atherosclerotic lesions and balloon injured arteries. Recently, we have devised a new strategy for anti-MCP-1 gene therapy by transfecting mutant MCP-1 gene into skeletal muscle. This mutant MCP-1 has been shown to work as a dominant-negative inhibitor of MCP-1. We here demonstrate that this strategy limited progression of pre-existing atherosclerotic lesions and improved the lesion composition into a more stable phenotype in the hypercholesterolemic mice. This strategy also suppressed monocyte infiltration/activation in the injured site and markedly inhibited restenotic changes (neointimal hyperplasia) in the carotid artery in rabbits, rats, and monkeys after balloon injury or stent implantation. Therefore, MCP-1-mediated monocyte infiltration is essential in the development of restenotic changes as well as atherosclerosis progression. MCP-1 can be a practical therapeutic target for human restenosis and atherosclerosis.