Vascular calcification inhibitors in relation to cardiovascular disease with special emphasis on fetuin-A in chronic kidney disease.
The mortality rate is extremely high in chronic kidney disease (CKD), primarily due to the high prevalence of cardiovascular disease (CVD) in this patient group. Apart from traditional Framingham risk factors, evidences suggest that nontraditional risk factors, such as inflammation, oxidative stress, endothelial dysfunction, and vascular calcification also contribute to this extremely high risk of CVD. Disturbance in the mineral metabolism, especially in the ions of Ca and PO4, are linked to enhanced calcification of blood vessels. Although the mechanism(s) of this enhanced calcification process are not fully understood, current knowledge suggests that a large number (and an imbalance between them) of circulating promoters and inhibitors of the calcification process, that is, fetuin-A (or alpha 2-Heremans-Schmid glycoprotein, AHSG), matrix-Gla protein (MGP), osteoprotegerin (OPG), osteopontin (OPN), bone morphogenetic proteins (BMPs), and inorganic pyrophosphate (PPi), are involved in the deterioration of vascular tissue. Thus, an imbalance in these factors may contribute to the high prevalence of vascular complications in CKD patients. Among these mediators, studies on fetuin-A deserve further attention as clinical studies consistently show that fetuin-A deficiency is associated with vascular calcification, all-cause and cardiovascular mortality in CKD patients. Both chronic inflammation and the uremic milieu per se may contribute to fetuin-A depletion, as well as specific mutations in the AHSG gene. Recent experimental and clinical studies also suggest an intriguing link between fetuin-A, insulin resistance, and the metabolic syndrome.
Suliman
Mohamed E
ME
Department of Clinical Science, Intervention and Technology, Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
García-López
Elvia
E
Anderstam
Björn
B
Lindholm
Bengt
B
Stenvinkel
Peter
P
D001798:Blood Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D055419:Bone Morphogenetic Protein 7 / Q000502:physiology; D002114:Calcinosis / Q000209:etiology / Q000517:prevention & control*; D002135:Calcium-Binding Proteins / Q000502:physiology; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D002908:Chronic Disease; D016326:Extracellular Matrix Proteins / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000209:etiology; D007674:Kidney Diseases / Q000150:complications*; D024821:Metabolic Syndrome / Q000209:etiology; D053495:Osteopontin / Q000502:physiology; D053244:Osteoprotegerin / Q000502:physiology; D014652:Vascular Diseases / Q000209:etiology / Q000517:prevention & control*; D060749:alpha-2-HS-Glycoprotein; D000097568:Matrix Gla Protein
D001798:Blood Proteins; D055419:Bone Morphogenetic Protein 7; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D053495:Osteopontin; D053244:Osteoprotegerin; D060749:alpha-2-HS-Glycoprotein; D000097568:Matrix Gla Protein; C556354:AHSG protein, human; C525819:BMP7 protein, human; C506030:TNFRSF11B protein, human