ADAM10 and ADAM17, Major Regulators of Chronic Kidney Disease Induced Atherosclerosis?

S.L. Maas*, M.M.P.C. Donners, E.P.C. van der Vorst*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

Abstract

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.
Original languageEnglish
Article number7309
Number of pages23
JournalInternational Journal of Molecular Sciences
Volume24
Issue number8
DOIs
Publication statusPublished - 1 Apr 2023

Keywords

  • a disintegrin and metalloprotease
  • chronic kidney disease
  • cardiovascular diseases
  • atherosclerosis
  • TUMOR-NECROSIS-FACTOR
  • ALPHA-CONVERTING-ENZYME
  • EPIDERMAL-GROWTH-FACTOR
  • FACTOR RECEPTOR TRANSACTIVATION
  • RENAL-TRANSPLANT DYSFUNCTION
  • TNF-ALPHA
  • MATRIX METALLOPROTEINASES
  • CELL-ADHESION
  • CARDIOVASCULAR-DISEASE
  • ENDOTHELIAL-CELLS

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