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ADAM10 and ADAM17, Major Regulators of Chronic Kidney Disease Induced Atherosclerosis?
Sanne L Maas1,2, Marjo M P C Donners3, Emiel P C van der Vorst1,2,4,5
1Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany.
Insights
Chronic kidney disease (CKD) accelerates cardiovascular disease (CVD) by causing systemic inflammation and altered bone metabolism. This review explores the role of ADAM10 and ADAM17 enzymes in the link between CKD and CVD.
Area of Science:
- Cardiovascular Science
- Nephrology
- Biochemistry
Background:
- Chronic kidney disease (CKD) affects millions globally, particularly those with hypertension and diabetes.
- CKD patients face significantly higher cardiovascular disease (CVD) risks due to accelerated atherosclerosis.
- CKD causes kidney damage, systemic inflammation, and altered mineral metabolism, contributing to vascular dysfunction and CVD.
Purpose of the Study:
- To review the roles of a disintegrin and metalloproteases (ADAM) 10 and ADAM17 in CKD and CVD.
- To investigate the function of ADAM10 and ADAM17 in CKD-induced CVD for the first time.
Main Methods:
- This narrative review synthesizes existing research on ADAM10 and ADAM17.
- Focuses on their known roles in cardiovascular disease and chronic kidney disease.
- Extrapolates their potential impact on the complex interplay between CKD and CVD.
Main Results:
- ADAM10 and ADAM17 are enzymes that cleave cell surface molecules, influencing cellular responses and releasing signaling molecules.
- Their specific roles in CVD and, to a lesser extent, CKD have been studied.
- Their precise contribution to CKD-induced CVD remains largely unelucidated.
Conclusions:
- ADAM10 and ADAM17 are critical regulators of cell surface interactions with potential roles in CKD-associated CVD.
- Further research is needed to fully understand their impact on CKD-induced cardiovascular complications.
- Elucidating these roles could reveal novel therapeutic targets for managing comorbid CKD and CVD.
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.
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