Glomerulosclerosis, arteriosclerosis, and vascular graft stenosis: Treatment with oral heparinoids

G. E. Striker, E. Lupia, Sharon Elliot, F. Zheng, C. McQuinn, C. Blagg, S. Selim, J. Vilar, L. J. Striker

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

At present there is no known treatment for established glomerulosclerosis or atherosclerosis. Since the principal lesion in glomerulosclerosis involves mesangial cells, a vascular smooth muscle cell, we searched for new therapeutic approaches affecting vascular smooth muscle function, especially with respect to modifying the turnover of extracellular matrix. We used mice transgenic for bovine growth hormone (bGH), since these mice develop end-stage renal disease due to progressive glomerulosclerosis. We previously showed that the subcutaneous injection of a non-anticoagulant heparin reduced glomerulosclerosis in bGH mice. Since injectable drugs are not a practical means of controlling glomerulosclerosis in humans, we assessed oral heparin-like compounds and found that oral pentosan polysulfate (PPS) reduced glomerulosclerosis in bGH mice at non-toxic doses. Because the positive therapeutic response in the bGH model could have been principally hormone-mediated, we examined other models of non-immune mediated glomerulosclerosis, including ROP Os/+ non-diabetic and diabetic mice. We found that an oral PPS (Elmiron), which is approved for other indications in humans, reduced sclerosis in all of these forms of chronic, progressive glomerulosclerosis. Based on the similarity of the cellular events in glomerulosclerosis and arteriosclerosis, we assessed the effect(s) of PPS in congenital (Watanabe rabbits) and induced (New Zealand White lipid-fed rabbits) models of arteriosclerosis. The extent and severity of the lesions was significantly reduced in both models by PPS treatment. Finally, we asked whether the proliferative and sclerotic lesion, which is the cause of vascular graft stenosis, might also respond to PPS treatment. To do this we cultured cells from the materials removed from stenotic arteriovenous grafts in hemodialysis patients. We found that PPS inhibits the proliferation and matrix production in a dose-dependent manner.

Original languageEnglish
JournalKidney International, Supplement
Volume51
Issue number63
StatePublished - Dec 1 1997
Externally publishedYes

Fingerprint

Pentosan Sulfuric Polyester
Heparinoids
Arteriosclerosis
Blood Vessels
Pathologic Constriction
Transplants
Vascular Smooth Muscle
Therapeutics
Heparin
Rabbits
Mesangial Cells
Sclerosis
Subcutaneous Injections
Transgenic Mice
Chronic Kidney Failure
Smooth Muscle Myocytes
Extracellular Matrix
Renal Dialysis
Cultured Cells
Atherosclerosis

Keywords

  • Atherosclerosis
  • Glomerulosclerosis
  • Heparinoid therapy
  • Pentosan polysulfate

ASJC Scopus subject areas

  • Nephrology

Cite this

Striker, G. E., Lupia, E., Elliot, S., Zheng, F., McQuinn, C., Blagg, C., ... Striker, L. J. (1997). Glomerulosclerosis, arteriosclerosis, and vascular graft stenosis: Treatment with oral heparinoids. Kidney International, Supplement, 51(63).

Glomerulosclerosis, arteriosclerosis, and vascular graft stenosis : Treatment with oral heparinoids. / Striker, G. E.; Lupia, E.; Elliot, Sharon; Zheng, F.; McQuinn, C.; Blagg, C.; Selim, S.; Vilar, J.; Striker, L. J.

In: Kidney International, Supplement, Vol. 51, No. 63, 01.12.1997.

Research output: Contribution to journalArticle

Striker, GE, Lupia, E, Elliot, S, Zheng, F, McQuinn, C, Blagg, C, Selim, S, Vilar, J & Striker, LJ 1997, 'Glomerulosclerosis, arteriosclerosis, and vascular graft stenosis: Treatment with oral heparinoids', Kidney International, Supplement, vol. 51, no. 63.
Striker, G. E. ; Lupia, E. ; Elliot, Sharon ; Zheng, F. ; McQuinn, C. ; Blagg, C. ; Selim, S. ; Vilar, J. ; Striker, L. J. / Glomerulosclerosis, arteriosclerosis, and vascular graft stenosis : Treatment with oral heparinoids. In: Kidney International, Supplement. 1997 ; Vol. 51, No. 63.
@article{54a770d05b9b4f74878f90707ceab764,
title = "Glomerulosclerosis, arteriosclerosis, and vascular graft stenosis: Treatment with oral heparinoids",
abstract = "At present there is no known treatment for established glomerulosclerosis or atherosclerosis. Since the principal lesion in glomerulosclerosis involves mesangial cells, a vascular smooth muscle cell, we searched for new therapeutic approaches affecting vascular smooth muscle function, especially with respect to modifying the turnover of extracellular matrix. We used mice transgenic for bovine growth hormone (bGH), since these mice develop end-stage renal disease due to progressive glomerulosclerosis. We previously showed that the subcutaneous injection of a non-anticoagulant heparin reduced glomerulosclerosis in bGH mice. Since injectable drugs are not a practical means of controlling glomerulosclerosis in humans, we assessed oral heparin-like compounds and found that oral pentosan polysulfate (PPS) reduced glomerulosclerosis in bGH mice at non-toxic doses. Because the positive therapeutic response in the bGH model could have been principally hormone-mediated, we examined other models of non-immune mediated glomerulosclerosis, including ROP Os/+ non-diabetic and diabetic mice. We found that an oral PPS (Elmiron), which is approved for other indications in humans, reduced sclerosis in all of these forms of chronic, progressive glomerulosclerosis. Based on the similarity of the cellular events in glomerulosclerosis and arteriosclerosis, we assessed the effect(s) of PPS in congenital (Watanabe rabbits) and induced (New Zealand White lipid-fed rabbits) models of arteriosclerosis. The extent and severity of the lesions was significantly reduced in both models by PPS treatment. Finally, we asked whether the proliferative and sclerotic lesion, which is the cause of vascular graft stenosis, might also respond to PPS treatment. To do this we cultured cells from the materials removed from stenotic arteriovenous grafts in hemodialysis patients. We found that PPS inhibits the proliferation and matrix production in a dose-dependent manner.",
keywords = "Atherosclerosis, Glomerulosclerosis, Heparinoid therapy, Pentosan polysulfate",
author = "Striker, {G. E.} and E. Lupia and Sharon Elliot and F. Zheng and C. McQuinn and C. Blagg and S. Selim and J. Vilar and Striker, {L. J.}",
year = "1997",
month = "12",
day = "1",
language = "English",
volume = "51",
journal = "Kidney International, Supplement",
issn = "0098-6577",
publisher = "Wiley-Blackwell",
number = "63",

}

TY - JOUR

T1 - Glomerulosclerosis, arteriosclerosis, and vascular graft stenosis

T2 - Treatment with oral heparinoids

AU - Striker, G. E.

AU - Lupia, E.

AU - Elliot, Sharon

AU - Zheng, F.

AU - McQuinn, C.

AU - Blagg, C.

AU - Selim, S.

AU - Vilar, J.

AU - Striker, L. J.

PY - 1997/12/1

Y1 - 1997/12/1

N2 - At present there is no known treatment for established glomerulosclerosis or atherosclerosis. Since the principal lesion in glomerulosclerosis involves mesangial cells, a vascular smooth muscle cell, we searched for new therapeutic approaches affecting vascular smooth muscle function, especially with respect to modifying the turnover of extracellular matrix. We used mice transgenic for bovine growth hormone (bGH), since these mice develop end-stage renal disease due to progressive glomerulosclerosis. We previously showed that the subcutaneous injection of a non-anticoagulant heparin reduced glomerulosclerosis in bGH mice. Since injectable drugs are not a practical means of controlling glomerulosclerosis in humans, we assessed oral heparin-like compounds and found that oral pentosan polysulfate (PPS) reduced glomerulosclerosis in bGH mice at non-toxic doses. Because the positive therapeutic response in the bGH model could have been principally hormone-mediated, we examined other models of non-immune mediated glomerulosclerosis, including ROP Os/+ non-diabetic and diabetic mice. We found that an oral PPS (Elmiron), which is approved for other indications in humans, reduced sclerosis in all of these forms of chronic, progressive glomerulosclerosis. Based on the similarity of the cellular events in glomerulosclerosis and arteriosclerosis, we assessed the effect(s) of PPS in congenital (Watanabe rabbits) and induced (New Zealand White lipid-fed rabbits) models of arteriosclerosis. The extent and severity of the lesions was significantly reduced in both models by PPS treatment. Finally, we asked whether the proliferative and sclerotic lesion, which is the cause of vascular graft stenosis, might also respond to PPS treatment. To do this we cultured cells from the materials removed from stenotic arteriovenous grafts in hemodialysis patients. We found that PPS inhibits the proliferation and matrix production in a dose-dependent manner.

AB - At present there is no known treatment for established glomerulosclerosis or atherosclerosis. Since the principal lesion in glomerulosclerosis involves mesangial cells, a vascular smooth muscle cell, we searched for new therapeutic approaches affecting vascular smooth muscle function, especially with respect to modifying the turnover of extracellular matrix. We used mice transgenic for bovine growth hormone (bGH), since these mice develop end-stage renal disease due to progressive glomerulosclerosis. We previously showed that the subcutaneous injection of a non-anticoagulant heparin reduced glomerulosclerosis in bGH mice. Since injectable drugs are not a practical means of controlling glomerulosclerosis in humans, we assessed oral heparin-like compounds and found that oral pentosan polysulfate (PPS) reduced glomerulosclerosis in bGH mice at non-toxic doses. Because the positive therapeutic response in the bGH model could have been principally hormone-mediated, we examined other models of non-immune mediated glomerulosclerosis, including ROP Os/+ non-diabetic and diabetic mice. We found that an oral PPS (Elmiron), which is approved for other indications in humans, reduced sclerosis in all of these forms of chronic, progressive glomerulosclerosis. Based on the similarity of the cellular events in glomerulosclerosis and arteriosclerosis, we assessed the effect(s) of PPS in congenital (Watanabe rabbits) and induced (New Zealand White lipid-fed rabbits) models of arteriosclerosis. The extent and severity of the lesions was significantly reduced in both models by PPS treatment. Finally, we asked whether the proliferative and sclerotic lesion, which is the cause of vascular graft stenosis, might also respond to PPS treatment. To do this we cultured cells from the materials removed from stenotic arteriovenous grafts in hemodialysis patients. We found that PPS inhibits the proliferation and matrix production in a dose-dependent manner.

KW - Atherosclerosis

KW - Glomerulosclerosis

KW - Heparinoid therapy

KW - Pentosan polysulfate

UR - http://www.scopus.com/inward/record.url?scp=0031307813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031307813&partnerID=8YFLogxK

M3 - Article

C2 - 9407438

AN - SCOPUS:0031307813

VL - 51

JO - Kidney International, Supplement

JF - Kidney International, Supplement

SN - 0098-6577

IS - 63

ER -