Department of Health Sciences, Renal Unit, "Magna Graecia" University, 88100 Catanzaro, Italy.
Division of Nephrology, University of Campania "Luigi Vanvitelli", 80100 Naples, Italy.
Biomolecules. 2020 Jan 17;10(1):154. doi: 10.3390/biom10010154.
Chronic Kidney Disease (CKD) represents a risk factor for fatal and nonfatal cardiovascular (CV) events, including peripheral vascular disease (PVD). This occurs because CKD encompasses several factors that lead to poor prognoses, mainly due to a reduction of the estimated glomerular filtration rate (eGFR), the presence of proteinuria, and the uremic inflammatory milieu. The matrix metalloproteinases (MMPs) are a group of zinc-containing endopeptidases implicated in extracellular matrix (ECM) remodeling, a systemic process in tissue homeostasis. MMPs play an important role in cell differentiation, angiogenesis, inflammation, and vascular damage. Our aim was to review the published evidence regarding the association between MMPs, PVD, and CKD to find possible common pathophysiological mechanisms. MMPs favor ECM deposition through the glomeruli, and start the shedding of cellular junctions and epithelial-mesenchymal transition in the renal tubules. MMP-2 and -9 have also been associated with the presence of systemic vascular damage, since they exert a pro-inflammatory and proatherosclerotic actions. An imbalance of MMPs was found in the context of PVD, where MMPs are predictors of poor prognoses in patients who underwent lower extremity revascularization. MMP circulating levels are increased in both conditions, i.e., that of CKD and PVD. A possible pathogenic link between these conditions is represented by the enhanced production of transforming growth factor-β that worsens vascular calcifications and atherosclerosis and the development of proteinuria in patients with increased levels of MMPs. Proteinuria has been recognized as a marker of systemic vascular damage, and this may explain in part the increase in CV risk that is manifest in patients with CKD and PVD. In conclusion, MMPs can be considered a useful tool by which to stratify CV risk in patients with CKD and PVD. Further studies are needed to investigate the causal-relationships between MMPs, CKD, and PVD, and to optimize their prognostic and predictive (in response to treatments) roles.
慢性肾脏病 (CKD) 是致命和非致命心血管 (CV) 事件的危险因素，包括外周血管疾病 (PVD)。这是因为 CKD 包含了导致预后不良的几个因素，主要是由于估计肾小球滤过率 (eGFR) 降低、蛋白尿的存在和尿毒症炎症环境。基质金属蛋白酶 (MMPs) 是一组含锌的内肽酶，参与细胞外基质 (ECM) 重塑，这是组织稳态的一个系统过程。MMPs 在细胞分化、血管生成、炎症和血管损伤中发挥重要作用。我们的目的是回顾已发表的关于 MMPs、PVD 和 CKD 之间关联的证据，以寻找可能的共同病理生理机制。MMPs 通过肾小球促进 ECM 沉积，并开始在肾小管中脱落细胞连接和上皮间质转化。MMP-2 和 -9 也与系统性血管损伤有关，因为它们具有促炎和促动脉粥样硬化作用。在 PVD 中发现了 MMPs 的不平衡，其中 MMPs 是接受下肢血运重建的患者预后不良的预测指标。在 CKD 和 PVD 这两种情况下，MMPs 的循环水平均升高。这些情况之间的一个可能的致病联系是转化生长因子-β的产生增加，这会加重血管钙化和动脉粥样硬化，并导致 MMPs 水平升高的患者出现蛋白尿。蛋白尿已被认为是系统性血管损伤的标志物，这可以部分解释在 CKD 和 PVD 患者中表现出的 CV 风险增加。总之，MMPs 可被视为评估 CKD 和 PVD 患者 CV 风险的有用工具。需要进一步研究以调查 MMPs、CKD 和 PVD 之间的因果关系，并优化其预后和预测（对治疗的反应）作用。
