Fetuin-A protects against atherosclerotic calcification in CKD.
نویسندگان
چکیده
Reduced serum levels of the calcification inhibitor fetuin-A associate with increased cardiovascular mortality in dialysis patients. Fetuin-A-deficient mice display calcification of various tissues but notably not of the vasculature. This absence of vascular calcification may result from the protection of an intact endothelium, which becomes severely compromised in the setting of atherosclerosis. To test this hypothesis, we generated fetuin-A/apolipoprotein E (ApoE)-deficient mice and compared them with ApoE-deficient and wild-type mice with regard to atheroma formation and extraosseous calcification. We assigned mice to three treatment groups for 9 wk: (1) Standard diet, (2) high-phosphate diet, or (3) unilateral nephrectomy (causing chronic kidney disease [CKD]) plus high-phosphate diet. Serum urea, phosphate, and parathyroid hormone levels were similar in all genotypes after the interventions. Fetuin-A deficiency did not affect the extent of aortic lipid deposition, neointima formation, and coronary sclerosis observed with ApoE deficiency, but the combination of fetuin-A deficiency, hyperphosphatemia, and CKD led to a 15-fold increase in vascular calcification in this model of atherosclerosis. Fetuin-A deficiency almost exclusively promoted intimal rather than medial calcification of atheromatous lesions. High-phosphate diet and CKD also led to an increase in valvular calcification and aorta-associated apoptosis, with wild-type mice having the least, ApoE-deficient mice intermediate, and fetuin-A/ApoE-deficient mice the most. In addition, the combination of fetuin-A deficiency, high-phosphate diet, and CKD in ApoE-deficient mice greatly enhanced myocardial calcification, whereas the absence of fetuin-A did not affect the incidence of renal calcification. In conclusion, fetuin-A inhibits pathologic calcification in both the soft tissue and vasculature, even in the setting of atherosclerosis.
منابع مشابه
Fetuin-mineral complex reflects extraosseous calcification stress in CKD.
Fetuin-A is an important inhibitor of extraosseous calcification, but some of the studies that used ELISAs did not identify a significant relationship between serum fetuin-A levels and vascular calcification in patients with chronic kidney disease (CKD). Here, we used centrifugation to separate a fetuin-mineral complex (FMC) composed of fetuin-A, fibrinogen, fibronectin-1, and calcium from the ...
متن کاملThe Role of Fetuin-A in Diabetes and Obesity: The Mechanism and Action
Fetuin-A is a phosphorylated glycoprotein produced by liver.It by binding to calcium ion inhibits ectopic calcium deposition and protects vascular calcification. Fetuin-A acts as a multifactorial protein and its role has been documented from brain development to bone remodeling and immune function, regulation of insulin activity, hepatocyte growth factor activity and inhibition lymphocyte blast...
متن کاملFetuin-A (AHSG) prevents extraosseous calcification induced by uraemia and phosphate challenge in mice.
BACKGROUND Chronic kidney disease (CKD) is associated with vascular and tissue calcification. The extent of vascular calcification has been identified as an independent risk factor of cardiovascular death in patients on haemodialysis. METHODS We studied the role of fetuin-A in CKD-associated calcification using a mouse model of graded renal insufficiency generated by nephrectomy and high phos...
متن کاملPhosphorylated fetuin-A-containing calciprotein particles are associated with aortic stiffness and a procalcific milieu in patients with pre-dialysis CKD.
BACKGROUND Vascular stiffening occurs in normal ageing and is accelerated in chronic kidney disease (CKD). Vascular calcification contributes to this stiffening and to the high incidence of vascular morbidity and mortality in this population. A network of inhibitors work in concert to reduce mineralization risk in extra-osseous tissue. Fetuin-A is an important systemic inhibitor of ectopic calc...
متن کاملFetuin-A is an independent determinant of change of aortic stiffness over 1 year in non-diabetic patients with CKD stages 3 and 4.
BACKGROUND Vascular calcification is highly prevalent in chronic kidney disease (CKD) patients. This calcification leads to arterial stiffening. Fetuin-A is an endogenous inhibitor of vascular calcification and has been associated with arterial stiffness and mortality in dialysis patients. We tested the relationship between fetuin-A and change in arterial stiffness in CKD stages 3 and 4. METH...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of the American Society of Nephrology : JASN
دوره 20 6 شماره
صفحات -
تاریخ انتشار 2009