Institute for Molecular Cardiovascular Research,Interdisciplinary Center for Clinical Research Aachen, RWTH Aachen University, Germany.
Curr Pharm Biotechnol. 2012 Jan;13(1):37-45. doi: 10.2174/138920112798868557.
Cardiovascular diseases, including atherosclerosis and the dreaded complication myocardial infarction, represent the major cause of death in western countries. It is now generally accepted that chemokines tightly control and modulate all the events which lead to initiation and progression of cardiovascular diseases, making them very attractive therapeutic targets for the pharmaceutical industry. Various studies showed until now the effects of antagonizing/ neutralizing chemokines or blocking chemokine receptors on cardiovascular pathology. The modulation of the CCL2/CCR2, CCL5/CCR1-CCR5, CXCL12/CXCR4 pathways by preventing receptor--ligand interaction, chemokine-glycosaminoglycan interaction, heteromerization, or interfering with the signaling pathways has proven to have high potential in future drug development. However, while trying to understand the effects of individual chemokines, the biologic consequences of multiple and concomitant chemokine expression on leukocyte migration and function should be taken into account as well. Therefore, many aspects should be considered and carefully scrutinized, when devising therapeutic strategies.
心血管疾病,包括动脉粥样硬化和可怕的并发症心肌梗死,是西方国家主要的死亡原因。现在普遍认为趋化因子严格控制和调节导致心血管疾病发生和发展的所有事件,使它们成为制药行业非常有吸引力的治疗靶点。直到现在,各种研究都显示了拮抗/中和趋化因子或阻断趋化因子受体对心血管病理学的影响。通过阻止受体-配体相互作用、趋化因子-糖胺聚糖相互作用、异源二聚体形成或干扰信号通路来调节 CCL2/CCR2、CCL5/CCR1-CCR5、CXCL12/CXCR4 途径,已被证明在未来药物开发中有很高的潜力。然而,在试图了解单个趋化因子的作用时,也应该考虑白细胞迁移和功能的多种趋化因子同时表达的生物学后果。因此,在制定治疗策略时,有许多方面需要考虑和仔细审查。