Biomedical subjects

Sharon M Moe

Publications and source records attributed to Sharon M Moe.

40 records · Page 3Linked to original sources

PubMed2002

Phosphorus and uremic serum up-regulate osteopontin expression in vascular smooth muscle cells.

BACKGROUND: Dialysis patients have accelerated atherosclerosis, with extensive calcification of both the intima and media. Cross-sectional studies have implicated hyperphosphatemia in this process, but the mechanism is unclear. METHODS: To test the hypothesis that hyperphosphatemia and/or uremia induces vascular calcification, bovine vascular smooth muscle cells (BVSMC) were treated with increasing concentrations of beta-glycerophosphate, a phosphate donor, in the presence or absence of inhibitors for sodium/phosphate (Na/Pi) co-transport (foscarnet) or alkaline phosphatase (levamisole) for 48 hours. BVSMC also were incubated for various times with DMEM plus 15% pooled uremic sera from patients with low (LP) or high serum phosphorus (HP), or from pooled healthy control serum. Calcification in BVSMC was examined by quantitation of calcium deposition. Osteopontin expression and alkaline phosphatase activity were assessed by Western blotting and a colorimetric assay. RESULTS: beta-glycerophosphate increased osteopontin expression and alkaline phosphatase activity in BVSMC. Inhibition of either alkaline phosphatase activity or Na/Pi co-transport abolished this effect. Compared to incubation with control human serum, BVSMC cultured with uremic sera had increased mineral deposition. Uremic sera also increased alkaline phosphatase activity and osteopontin expression in BVSMC. The addition of beta-glycerophosphate to uremic HP or LP sera did not further augment osteopontin expression. Blocking Na/Pi co-transport or alkaline phosphatase activity only partially inhibited uremic sera-induced osteopontin expression, indicating that other non-Na/Pi co-transport dependent mechanisms also are involved. CONCLUSION: beta-glycerophosphate and uremic sera induce calcification and osteopontin expression in BVSMC. The uremic sera-induced osteopontin expression in BVSMC is partially mediated through alkaline phosphatase activity and a Na/Pi co-transporter dependent mechanism. However, other non-Na/Pi dependent mechanisms also contribute to accelerated vascular calcification in patients with ESRD.

Alkaline Phosphatase↗

PubMed2002

[Vascular calcification in end stage renal disease].

Vascular calcification is thought to play a crucial role in the excessive cardiovascular mortality and morbidity in patients with end-stage renal disease (ESRD). Recent evidence suggests that uremic vascular calcification is an active cell-mediated process resembling osteogenesis in bone, rather than passive precipitation of calcium and phosphorus in the setting of deranged mineral metabolism. To date, several bone-associated proteins (osteopontin, bone sialoprotein, alkaline phosphatase, type I collagen) have been demonstrated in histological sections of vessels obtained from patients with ESRD or calcific uremic arteriolopathy. In in vitro experiments, addition of uremic serum upregulates osteopontin expression by cultured vascular smooth muscle cells. We are only beginning to understand the process by which vascular smooth muscle cells transform into osteoblast-like cells, although phosphorus may play a key role. Additional factors mediating or modulating development of vascular calcification in ESRD remain to be identified. Further understanding of the pathophysiology of uremic vascular calcification is needed to design effective therapeutic strategies to intervene with this devastating condition in ESRD population.

Journal Article↗

PubMedDate not supplied

The role of vitamin D in vascular calcification in chronic kidney disease.

Vascular calcification is a significant cause of morbidity and mortality in patients with chronic kidney disease (CKD). Disorders of mineral metabolism are likely involved in the pathogenesis of vascular calcification. Calcitriol and its analogs are effective in suppressing parathyroid hormone levels in patients with secondary hyperparathyroidism and CKD, but experimental studies demonstrate that these drugs can act directly on vascular smooth muscle cells. In some in vitro studies and in animal models of CKD, calcitriol has induced vascular calcification. Newer analogs of vitamin D appear to be less likely to induce vascular calcification, although published data are scarce. However, there is really no clear evidence in dialysis patients that calcitriol or analog administration is directly responsible for the induction of vascular calcification. However, indirectly, by oversuppression of parathyroid hormone (PTH) and induction of a low-turnover bone disease state, or by increased calcium-phosphorus product, the administration of calcitriol or its analogs may contribute to vascular calcification in patients with CKD. However, prospective randomized trials in CKD patients are necessary to fully understand the impact of calcitriol and analog therapy on vascular calcification.

Animals↗

PubMedDate not supplied

Management of renal osteodystrophy in peritoneal dialysis patients.

The term "renal osteodystrophy" encompasses all forms of metabolic bone disease found in dialysis patients. The primary approach to the treatment of renal osteodystrophy in peritoneal dialysis (PD) patients is similar to that in hemodialysis patients. However, the increased prevalence of adynamic bone histology, together with the difficulty in judging calcium balance, the inability to practicably give intravenous vitamin D, and the clearance of vitamin D and parathyroid hormone via dialysate require a different therapeutic approach in PD compared to hemodialysis patients. Clearly, more comparative studies of new agents are needed to find the optimal approach to achieving the K/DOQI guidelines in PD patients. The unique aspects of the approach to renal osteodystrophy in PD patients are the focus of this review.

Chronic Kidney Disease-Mineral and Bone Disorder↗