Pathophysiological mechanisms and consequences of cardiovascular calcifications: role of uremic toxicity.
Chronic kidney disease (CKD) represents an accelerated model of the active cardiovascular calcification process. Recent data from our laboratory indicate the presence of a possible vascular remodeling leading to vascular calcification similar to that observed in bone tissue, and emphasize the role of uremic toxicity. Uremic serum not only induces differentiation of smooth muscle cells into an osteoblast-like phenotype but also inhibits the differentiation of monocyte-macrophages cells into osteoclasts. The imbalance between the two processes in vascular walls in favor of osteoblast-like formation could lead to calcification. Cardiovascular calcification may contribute to the high rate of cardiovascular disease in patients with CKD. However, uremic toxicity, which participates in the pathogenesis of cardiovascular calcification, seems to have independent effects on vascular walls, at least in the early stages of CKD. We recently reported that functional (i.e. endothelial dysfunction) rather than structural changes, including vascular calcification, may contribute to the aortic hemodynamic changes observed during early CKD. Uremic toxicity also appears to be associated with calcification of intracranial arteries. Knowledge concerning the pathogenesis and consequences of cardiovascular calcification derived from the uremic model therefore opens up new perspectives for pharmacologic treatments that may also help to prevent and/or treat cardiovascular calcification, and consequently cardiovascular mortality and morbidity, not only in CKD patients but also in the general population.
Chillon
J-M
JM
Inserm ERI-12, Amiens, France.
Mozar
A
A
Six
I
I
Maizel
J
J
Bugnicourt
J-M
JM
Kamel
S
S
Slama
M
M
Brazier
M
M
Massy
Z A
ZA
D002114:Calcinosis / Q000473:pathology* / Q000628:therapy; D002318:Cardiovascular Diseases / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000473:pathology*; D014511:Uremia / Q000150:complications / Q000473:pathology*