Abstract: SA-PO860

BMP7 Ameliorates Procalcific Gene Expression Patterns in the Calcified Uremic Aorta

Session Information

  • Vascular Calcification
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Mineral Disease

  • 1205 Vascular Calcification

Authors

  • Gravesen, Eva, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • Mace, Maria Lerche, Herlev Hospital, Copenhagen, Denmark
  • Nordholm, Anders, Herlev Hospital, Copenhagen, Denmark
  • Hofman-Bang, Jacob, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • Hruska, Keith A., Washington University St. Louis, St. Louis, Missouri, United States
  • Olgaard, Klaus, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • Lewin, Ewa, Herlev Hospital, Copenhagen, Denmark
Background

Hyperphosphatemia and vascular calcification(VC) are frequent complications of chronic renal failure(CRF). BMP7 has been shown to protect against development of VC in uremia. Thus the potential reversibility of established VC was examined in two experimental models; 1. by studying if BMP7 treatment could reduce the degree of VC in uremia and 2. by isogenic transplantation(ATx) of the calcified aorta from uremic rats to healthy littermates.

Methods

CRF and VC was induced in adult DA-rats by 5/6 nephrectomy, high phosphate(P) diet and alfacalcidol treatment. After 14 wks, severe VC was present. In model 1, CRF rats were allocated either to 250µg/kg of BMP7 ip once weekly or vehicle for 8 wks. In model 2, the abdominal aorta was transplanted orthotopically from CRF rats to healthy littermates. Ctrl group had normal to normal ATx. Rats were sacrificed 4 wks after ATx.

Results

BMP7 treatment resulted in a significant reduction of plasma P from 2.06±0.14 to 1.56±0.07mmol/L, p<0.01, despite persistent uremia. Uremia induced increase in aortic expression of fibronectin 1.15±0.11, periostin 1.31±0.14 and activin-A 1.34±0.06, and BMP7 treatment resulted in a significant decrease; Fn1 0.82±0.09, Postn 0.91±0.09, Inhiba 0.97±0.11, p<0.05. In the BMP7 study Ca content was significantly increased in the uremic vehicle treated rats both in the distal abdominal aorta 1.9±0.2µg/mg and in the proximal thoracic aorta 71±11µg/mg, and similar levels were seen in the BMP7 treated rats; 2.2±0.2µg/mg in the distal abdominal aorta and 54±7µg/mg in the proximal thoracic aorta.
In the ATx study Ca content of the aorta from uremic rats was significantly elevated to 17.0±0.2µg/mg in the proximal abdominal aorta and similarly increased in the transplanted uremic aorta 15.9±0.6µg/mg, confirming that established uremic VC is not reversible despite removal of the uremic milieu.

Conclusion

BMP7 treatment resulted in a significant decrease in the expression of procalcific genes and a siginificant decrease in plasma P. Despite these favorable changes no effect on aortic Ca content was seen. These results were confirmed in the ATx study, where complete reversal of the uremic mileu neither reversed established uremic VC.

Funding

  • Private Foundation Support