Sluijter Joost P G, de Kleijn Dominique P V, Pasterkamp Gerard
Experimental Cardiology Laboratory, Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, Room G02-523, 3584 CX Utrecht, The Netherlands.
Cardiovasc Res. 2006 Feb 15;69(3):595-603. doi: 10.1016/j.cardiores.2005.11.026. Epub 2006 Jan 4.
Physiological and pathological tissue remodeling needs an orderly degradation of the extracellular matrix. Matrix metalloproteinases (MMPs) are proteases capable of degrading different extracellular matrix components, including collagen and elastin. MMP expression is strongly enhanced in vascular pathologies such as stenosis following balloon dilation, in-stent restenosis, sustained flow changes, aneurysm formation, and atherosclerosis. Experimental studies have revealed that some biological actions of MMPs aggravate a pathological condition, whereas others may be beneficial for the patient suffering from atherosclerotic disease. Therefore, a better understanding of the biological consequence and regulation of MMP activity is critical for the design and potential application of specific MMP inhibitors in vascular disease. In this review, we will give an overview of preclinical experimental studies using MMP inhibitors with the objective to influence vascular occlusive diseases, and we will also highlight new targets that influence MMP expression and activity and that possess potential for therapeutic interventions.
生理和病理组织重塑需要细胞外基质的有序降解。基质金属蛋白酶（MMPs）是能够降解不同细胞外基质成分（包括胶原蛋白和弹性蛋白）的蛋白酶。在血管病变如球囊扩张后狭窄、支架内再狭窄、持续血流变化、动脉瘤形成和动脉粥样硬化中，MMP表达会显著增强。实验研究表明，MMPs的一些生物学作用会加重病理状况，而其他作用可能对患有动脉粥样硬化疾病的患者有益。因此，更好地理解MMP活性的生物学后果和调控对于设计和潜在应用特定的MMP抑制剂治疗血管疾病至关重要。在本综述中，我们将概述使用MMP抑制剂以影响血管闭塞性疾病的临床前实验研究，并且我们还将强调影响MMP表达和活性且具有治疗干预潜力的新靶点。
