Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, São Paulo, Brazil.
Basic Clin Pharmacol Toxicol. 2012 May;110(5):409-15. doi: 10.1111/j.1742-7843.2012.00863.x. Epub 2012 Mar 2.
End-stage kidney disease (ESKD) is a major health problem associated with very high morbidity and mortality secondary to cardiovascular complications, especially in ESKD patients on dialysis. Therefore, exploring key mechanisms underlying cardiovascular alterations associated with ESKD may offer reasonable pharmacological targets that may benefit these patients. Imbalanced matrix metalloproteinases (MMP) activities have been implicated in many cardiovascular diseases, and growing evidence now indicates that excessive MMP activities contribute to cardiovascular complications in ESKD patients. However, there is no study on the effects of MMP inhibitors (MMPIs) in such patients. MMPIs may prevent against the vascular and cardiac changes associated with ESKD. In this MiniReview, we aimed at reviewing current evidence supporting the idea that pharmacological inhibition of imbalanced MMP activities in ESKD may decrease the morbidity and mortality associated with cardiovascular complications in ESKD patients. However, MMPs have variable effects during different phases of kidney disease, and therefore optimal timing for MMP inhibition during a disease process may vary significantly and is largely undetermined. While current research shows that MMPs play a role in the pathogenesis of the cardiovascular alterations found in ESKD patients, clinical studies are required to validate the idea of using MMPIs in ESKD.
终末期肾病(ESKD)是一个主要的健康问题,与心血管并发症相关的发病率和死亡率非常高,尤其是在透析的 ESKD 患者中。因此,探索与 ESKD 相关的心血管改变的关键机制可能提供合理的药理靶点,使这些患者受益。失衡的基质金属蛋白酶(MMP)活性与许多心血管疾病有关,越来越多的证据表明,MMP 活性的过度增加导致 ESKD 患者的心血管并发症。然而,目前还没有关于 MMP 抑制剂(MMPI)在这些患者中的作用的研究。MMPI 可能预防与 ESKD 相关的血管和心脏变化。在这个 MiniReview 中,我们旨在回顾目前支持这样一种观点的证据,即药理抑制 ESKD 中失衡的 MMP 活性可能降低与 ESKD 患者心血管并发症相关的发病率和死亡率。然而,MMP 在肾脏疾病的不同阶段有不同的作用,因此,在疾病过程中 MMP 抑制的最佳时机可能有很大的差异,并且在很大程度上还没有确定。虽然目前的研究表明 MMP 在 ESKD 患者心血管改变的发病机制中起作用,但需要进行临床研究来验证使用 MMPIs 治疗 ESKD 的想法。