Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany.
Aachen-Maastricht Institute for CardioRenal Disease (AMICARE), RWTH Aachen University, 52074 Aachen, Germany.
Int J Mol Sci. 2023 Apr 15;24(8):7309. doi: 10.3390/ijms24087309.
Chronic kidney disease (CKD) is a major health problem, affecting millions of people worldwide, in particular hypertensive and diabetic patients. CKD patients suffer from significantly increased cardiovascular disease (CVD) morbidity and mortality, mainly due to accelerated atherosclerosis development. Indeed, CKD not only affects the kidneys, in which injury and maladaptive repair processes lead to local inflammation and fibrosis, but also causes systemic inflammation and altered mineral bone metabolism leading to vascular dysfunction, calcification, and thus, accelerated atherosclerosis. Although CKD and CVD individually have been extensively studied, relatively little research has studied the link between both diseases. This narrative review focuses on the role of a disintegrin and metalloproteases (ADAM) 10 and ADAM17 in CKD and CVD and will for the first time shed light on their role in CKD-induced CVD. By cleaving cell surface molecules, these enzymes regulate not only cellular sensitivity to their micro-environment (in case of receptor cleavage), but also release soluble ectodomains that can exert agonistic or antagonistic functions, both locally and systemically. Although the cell-specific roles of ADAM10 and ADAM17 in CVD, and to a lesser extent in CKD, have been explored, their impact on CKD-induced CVD is likely, yet remains to be elucidated.
慢性肾脏病(CKD)是一个主要的健康问题,影响着全世界数以百万计的人,尤其是高血压和糖尿病患者。CKD 患者的心血管疾病(CVD)发病率和死亡率显著增加,主要是由于动脉粥样硬化发展加速。事实上,CKD 不仅影响肾脏,在肾脏中,损伤和适应性修复过程导致局部炎症和纤维化,而且还导致全身炎症和矿物质骨代谢改变导致血管功能障碍、钙化,从而加速动脉粥样硬化。尽管 CKD 和 CVD 都已经得到了广泛的研究,但相对较少的研究关注这两种疾病之间的联系。这篇综述重点介绍了解整合素和金属蛋白酶(ADAM)10 和 ADAM17 在 CKD 和 CVD 中的作用,并首次阐明了它们在 CKD 引起的 CVD 中的作用。这些酶通过切割细胞表面分子,不仅调节细胞对其微环境的敏感性(在受体切割的情况下),而且还释放可溶性细胞外结构域,这些结构域可以发挥局部和全身的激动或拮抗作用。尽管 ADAM10 和 ADAM17 在 CVD 中的细胞特异性作用以及在 CKD 中的作用较小已经得到了探索,但它们对 CKD 引起的 CVD 的影响可能仍然需要阐明。
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