ADAM10 and ADAM17, Major Regulators of Chronic Kidney Disease Induced Atherosclerosis?
Sanne L MaasMarjo M P C DonnersEmiel P.C. van der VorstPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- chronic kidney disease
- end stage renal disease
- cardiovascular disease
- high glucose
- diabetic rats
- oxidative stress
- public health
- healthcare
- bone marrow
- multidrug resistant
- blood pressure
- endothelial cells
- type diabetes
- peritoneal dialysis
- single cell
- bone mineral density
- body composition
- cell therapy
- risk assessment
- patient reported