Renal and Vascular Inflammation, IIS-Fundacion Jimenez Diaz, Autonoma University, Madrid, Spain.
Cardiovasc Ther. 2012 Aug;30(4):e189-97. doi: 10.1111/j.1755-5922.2011.00274.x. Epub 2011 Apr 1.
Prevention and treatment of atherosclerosis is still a clinical challenge in the cardiovascular medicine. The classical belief that atherosclerotic lesion development solely depends on lipid deposition has been replaced by the current concept that activation of immune and inflammatory responses plays a central role in plaque initiation and progression. In this review we summarize studies on human and genetically modified animals describing a finite number of cellular and molecular mechanisms that underlie immunoinflammation in atherosclerotic plaques. We focus on the pro- and antiinflammatory mediators activated during atherogenesis and the intracellular signaling pathways regulating these events. Besides the advances on established pharmacological agents, we propose potential strategies for reduction/stabilization of atherosclerotic plaques based on the clinical data in inflammatory-associated pathologies and on the encouraging studies in experimental models of atherosclerosis. We emphasize the potential of such novel inhibitors comprising receptor antagonists, neutralizing antibodies, kinase inhibitors, peptide-based technologies, and chemicals as emerging antiinflammatory strategies for the treatment of atherosclerotic disease complications.
动脉粥样硬化的预防和治疗仍然是心血管医学的临床挑战。目前的观念认为，免疫和炎症反应的激活在斑块的起始和进展中起着核心作用，取代了过去认为动脉粥样硬化病变的发展仅取决于脂质沉积的经典观念。在这篇综述中，我们总结了描述在动脉粥样硬化斑块中免疫炎症基础的有限数量的细胞和分子机制的人类和基因修饰动物的研究。我们专注于在动脉粥样发生过程中激活的促炎和抗炎介质，以及调节这些事件的细胞内信号通路。除了在已确立的药理学制剂方面的进展之外，我们还根据与炎症相关的病理学中的临床数据和在动脉粥样硬化实验模型中的令人鼓舞的研究，提出了基于减少/稳定动脉粥样硬化斑块的潜在策略。我们强调了这些新型抑制剂的潜力，包括受体拮抗剂、中和抗体、激酶抑制剂、基于肽的技术和化学物质，作为治疗动脉粥样硬化疾病并发症的新兴抗炎策略。
