Increased vascular growth in hemodialysis patients induced by platelet-derived diadenosine polyphosphates

J Jankowski; J Hagemann; M S Yoon; M van der Giet; N Stephan; W Zidek; H Schlüter; M Tepel

doi:10.1046/j.1523-1755.2001.0590031134.x

Increased vascular growth in hemodialysis patients induced by platelet-derived diadenosine polyphosphates

Standard

Increased vascular growth in hemodialysis patients induced by platelet-derived diadenosine polyphosphates. / Jankowski, J; Hagemann, J; Yoon, M S; van der Giet, M; Stephan, N; Zidek, W; Schlüter, H; Tepel, M.

In: KIDNEY INT, Vol. 59, No. 3, 03.2001, p. 1134-41.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Jankowski, J, Hagemann, J, Yoon, MS, van der Giet, M, Stephan, N, Zidek, W, Schlüter, H & Tepel, M 2001, 'Increased vascular growth in hemodialysis patients induced by platelet-derived diadenosine polyphosphates', KIDNEY INT, vol. 59, no. 3, pp. 1134-41. https://doi.org/10.1046/j.1523-1755.2001.0590031134.x

APA

Jankowski, J., Hagemann, J., Yoon, M. S., van der Giet, M., Stephan, N., Zidek, W., Schlüter, H., & Tepel, M. (2001). Increased vascular growth in hemodialysis patients induced by platelet-derived diadenosine polyphosphates. KIDNEY INT, 59(3), 1134-41. https://doi.org/10.1046/j.1523-1755.2001.0590031134.x

Vancouver

Jankowski J, Hagemann J, Yoon MS, van der Giet M, Stephan N, Zidek W et al. Increased vascular growth in hemodialysis patients induced by platelet-derived diadenosine polyphosphates. KIDNEY INT. 2001 Mar;59(3):1134-41. https://doi.org/10.1046/j.1523-1755.2001.0590031134.x

Bibtex

@article{46149b15b6a44d238a2d257b2c1fc33a,

title = "Increased vascular growth in hemodialysis patients induced by platelet-derived diadenosine polyphosphates",

abstract = "BACKGROUND: Enhanced vascular smooth muscle cell (VSMC) growth is one hallmark of atherosclerosis. One mechanism responsible for stimulating arterial smooth muscle cell growth is the release of growth factors from platelets aggregating at endothelial lesions. Since in end-stage renal failure (ESRF) atherogenesis is markedly accelerated, the release of VSMC growth factors on aggregation of platelets from hemodialysis patients, ESRF patients in the predialysis stage, and healthy subjects was examined.METHODS: Platelets were activated by thrombin, and the supernatant was tested for growth stimulation in VSMCs from rat aorta. The cell proliferation rate was determined by [(3)H]-thymidine incorporation in VSMCs. The diadenosine polyphosphate (Ap(n)A with N = 3 to 6) content in the supernatant and in intact platelets was determined using a chromatographic assay established on the basis of affinity- and reversed-phase chromatographic methods.RESULTS: The thrombin-activated platelet supernatant from hemodialysis patients (N = 15) increased the [(3)H]-thymidine incorporation rate in VSMC s in comparison to the supernatant of healthy control subjects (N = 17, counts/supernatant of 10(6) stimulated platelets +/- SEM, 604 +/- 71 vs. 364 +/- 45, P < 0.05). The addition of the selective P2-receptor blocker pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid to supernatants inhibited the stimulatory effects of Ap(n)A on the growth of vascular smooth muscle cells (219 +/- 53 vs. 156 +/- 71 counts/supernatant of 106 stimulated platelets +/- SEM). The Ap(n)A (N = 3 to 6) amount of thrombin-activated platelet supernatants from hemodialysis patients was significantly higher than in platelets from 10 healthy control subjects (Ap(3)A, 119 +/- 32 vs. 12 +/- 3; Ap(4)A, 154 +/- 59 vs. 43 +/- 20; Ap(5)A, 39 +/- 14 vs. 13 +/- 6; Ap(6)A, 42 +/- 19 vs. 2 +/- 1 fg/platelet +/- SEM, each P < 0.05, N = 10). The intracellular Ap(n)A (N = 3 to 6) amount of intact platelets from hemodialysis patients (N = 61) was significantly higher than that from healthy control subjects [N = 30, Ap(n)A amount (fg/platelet +/- SEM): Ap(3)A, 366 +/- 68 vs. 14.7 +/- 1; Ap(4)A, 336 +/- 48 vs. 19 +/- 2; Ap(5)A, 227 +/- 35 vs. 10 +/- 1; Ap(6)A, 141 +/- 45 vs. 4 +/- 1; each P < 0.01].CONCLUSIONS: The increased amount of dinucleoside polyphosphate in platelets from hemodialysis patients may be an important additional atherogenic factor.",

keywords = "Animals, Blood Platelets, Cell Division, Cells, Cultured, Dinucleoside Phosphates, Female, Humans, Kidney Failure, Chronic, Male, Middle Aged, Muscle, Smooth, Vascular, Neovascularization, Pathologic, Rats, Rats, Inbred WKY, Reference Values, Renal Dialysis, Thrombin, Thymidine, Journal Article, Research Support, Non-U.S. Gov't",

author = "J Jankowski and J Hagemann and Yoon, {M S} and {van der Giet}, M and N Stephan and W Zidek and H Schl{\"u}ter and M Tepel",

year = "2001",

month = mar,

doi = "10.1046/j.1523-1755.2001.0590031134.x",

language = "English",

volume = "59",

pages = "1134--41",

journal = "KIDNEY INT",

issn = "0085-2538",

publisher = "NATURE PUBLISHING GROUP",

number = "3",

}

RIS

TY - JOUR

T1 - Increased vascular growth in hemodialysis patients induced by platelet-derived diadenosine polyphosphates

AU - Jankowski, J

AU - Hagemann, J

AU - Yoon, M S

AU - van der Giet, M

AU - Stephan, N

AU - Zidek, W

AU - Schlüter, H

AU - Tepel, M

PY - 2001/3

Y1 - 2001/3

N2 - BACKGROUND: Enhanced vascular smooth muscle cell (VSMC) growth is one hallmark of atherosclerosis. One mechanism responsible for stimulating arterial smooth muscle cell growth is the release of growth factors from platelets aggregating at endothelial lesions. Since in end-stage renal failure (ESRF) atherogenesis is markedly accelerated, the release of VSMC growth factors on aggregation of platelets from hemodialysis patients, ESRF patients in the predialysis stage, and healthy subjects was examined.METHODS: Platelets were activated by thrombin, and the supernatant was tested for growth stimulation in VSMCs from rat aorta. The cell proliferation rate was determined by [(3)H]-thymidine incorporation in VSMCs. The diadenosine polyphosphate (Ap(n)A with N = 3 to 6) content in the supernatant and in intact platelets was determined using a chromatographic assay established on the basis of affinity- and reversed-phase chromatographic methods.RESULTS: The thrombin-activated platelet supernatant from hemodialysis patients (N = 15) increased the [(3)H]-thymidine incorporation rate in VSMC s in comparison to the supernatant of healthy control subjects (N = 17, counts/supernatant of 10(6) stimulated platelets +/- SEM, 604 +/- 71 vs. 364 +/- 45, P < 0.05). The addition of the selective P2-receptor blocker pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid to supernatants inhibited the stimulatory effects of Ap(n)A on the growth of vascular smooth muscle cells (219 +/- 53 vs. 156 +/- 71 counts/supernatant of 106 stimulated platelets +/- SEM). The Ap(n)A (N = 3 to 6) amount of thrombin-activated platelet supernatants from hemodialysis patients was significantly higher than in platelets from 10 healthy control subjects (Ap(3)A, 119 +/- 32 vs. 12 +/- 3; Ap(4)A, 154 +/- 59 vs. 43 +/- 20; Ap(5)A, 39 +/- 14 vs. 13 +/- 6; Ap(6)A, 42 +/- 19 vs. 2 +/- 1 fg/platelet +/- SEM, each P < 0.05, N = 10). The intracellular Ap(n)A (N = 3 to 6) amount of intact platelets from hemodialysis patients (N = 61) was significantly higher than that from healthy control subjects [N = 30, Ap(n)A amount (fg/platelet +/- SEM): Ap(3)A, 366 +/- 68 vs. 14.7 +/- 1; Ap(4)A, 336 +/- 48 vs. 19 +/- 2; Ap(5)A, 227 +/- 35 vs. 10 +/- 1; Ap(6)A, 141 +/- 45 vs. 4 +/- 1; each P < 0.01].CONCLUSIONS: The increased amount of dinucleoside polyphosphate in platelets from hemodialysis patients may be an important additional atherogenic factor.

AB - BACKGROUND: Enhanced vascular smooth muscle cell (VSMC) growth is one hallmark of atherosclerosis. One mechanism responsible for stimulating arterial smooth muscle cell growth is the release of growth factors from platelets aggregating at endothelial lesions. Since in end-stage renal failure (ESRF) atherogenesis is markedly accelerated, the release of VSMC growth factors on aggregation of platelets from hemodialysis patients, ESRF patients in the predialysis stage, and healthy subjects was examined.METHODS: Platelets were activated by thrombin, and the supernatant was tested for growth stimulation in VSMCs from rat aorta. The cell proliferation rate was determined by [(3)H]-thymidine incorporation in VSMCs. The diadenosine polyphosphate (Ap(n)A with N = 3 to 6) content in the supernatant and in intact platelets was determined using a chromatographic assay established on the basis of affinity- and reversed-phase chromatographic methods.RESULTS: The thrombin-activated platelet supernatant from hemodialysis patients (N = 15) increased the [(3)H]-thymidine incorporation rate in VSMC s in comparison to the supernatant of healthy control subjects (N = 17, counts/supernatant of 10(6) stimulated platelets +/- SEM, 604 +/- 71 vs. 364 +/- 45, P < 0.05). The addition of the selective P2-receptor blocker pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid to supernatants inhibited the stimulatory effects of Ap(n)A on the growth of vascular smooth muscle cells (219 +/- 53 vs. 156 +/- 71 counts/supernatant of 106 stimulated platelets +/- SEM). The Ap(n)A (N = 3 to 6) amount of thrombin-activated platelet supernatants from hemodialysis patients was significantly higher than in platelets from 10 healthy control subjects (Ap(3)A, 119 +/- 32 vs. 12 +/- 3; Ap(4)A, 154 +/- 59 vs. 43 +/- 20; Ap(5)A, 39 +/- 14 vs. 13 +/- 6; Ap(6)A, 42 +/- 19 vs. 2 +/- 1 fg/platelet +/- SEM, each P < 0.05, N = 10). The intracellular Ap(n)A (N = 3 to 6) amount of intact platelets from hemodialysis patients (N = 61) was significantly higher than that from healthy control subjects [N = 30, Ap(n)A amount (fg/platelet +/- SEM): Ap(3)A, 366 +/- 68 vs. 14.7 +/- 1; Ap(4)A, 336 +/- 48 vs. 19 +/- 2; Ap(5)A, 227 +/- 35 vs. 10 +/- 1; Ap(6)A, 141 +/- 45 vs. 4 +/- 1; each P < 0.01].CONCLUSIONS: The increased amount of dinucleoside polyphosphate in platelets from hemodialysis patients may be an important additional atherogenic factor.

KW - Animals

KW - Blood Platelets

KW - Cell Division

KW - Cells, Cultured

KW - Dinucleoside Phosphates

KW - Female

KW - Humans

KW - Kidney Failure, Chronic

KW - Male

KW - Middle Aged

KW - Muscle, Smooth, Vascular

KW - Neovascularization, Pathologic

KW - Rats

KW - Rats, Inbred WKY

KW - Reference Values

KW - Renal Dialysis

KW - Thrombin

KW - Thymidine

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1046/j.1523-1755.2001.0590031134.x

DO - 10.1046/j.1523-1755.2001.0590031134.x

M3 - SCORING: Journal article

C2 - 11231371

VL - 59

SP - 1134

EP - 1141

JO - KIDNEY INT

JF - KIDNEY INT

SN - 0085-2538

IS - 3

ER -