Inhibition of restenosis lesion formation in the swine coronary artery by dietary potassium

Young, David B.; Srivastava, Neetu; Anderson, Peter G.; Ma, Gil; Skelton, T.N.; Grady, Andrew W.

doi:10.1016/s0895-7061(97)90741-x

Cited by 2 publications

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“…Similarly, DNA synthesis stimulated by bFGF (25 ng/mL in DMEM) was inhibited by increases in potassium concentration (P Ͻ .01 ANOVA, r ϭ Ϫ0.47, P Ͻ .01) shown in Figure 2B. 3 H-thymidine incorporation ranged from 106 Ϯ 6% in potassium concentration of 3 mmol/L to 76 Ϯ 5% in potassium concentration of 6 mmol/L. A significant inverse relation was found between potassium concentration and thymidine incorporation in cells stimulated by 5% FBS as well (P Ͻ .01 ANOVA, r ϭ Ϫ0.62, P Ͻ .01), shown in Fig.…”

Section: Effect Of Potassium Concentration On Vascularmentioning

confidence: 72%

“…2C. 3 H-thymidine incorporation ranged from 111 Ϯ 4% in potassium concentration of 3 mmol/L to 81 Ϯ 3% in potassium concentration of 6 mmol/L (P Ͻ .01 v potassium concentration of 4 mmol/L). Thus, physiologic elevation of potassium concentration opposes the effect of PDGF-BB, bFGF, and serum cytokines to stimulate DNA synthesis.…”

Section: Effect Of Potassium Concentration On Vascularmentioning

confidence: 99%

“…Stimulation of DNA synthesis was measured by analyzing the incorporation of [methyl 3 H] thymidine. Vascular smooth muscle cells were seeded at a density of 35,000 cells/mL (for PDGF-BB, bFGF studies) or 25,000 cells/mL (for 5% FBS study) in 12-well plates and allowed to attach and become quiescent for 48 h in serum-free DMEM to arrest growth of the cells in the G 0 phase of the cell cycle.…”

Section: Dna Synthesismentioning

confidence: 99%

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Increased potassium concentration inhibits stimulation of vascular smooth muscle proliferation by PDGF-BB and bFGF

Mamaril

Young

2000

American Journal of Hypertension

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In normal rabbits on a high-cholesterol diet we observed that reducing dietary potassium intake from normal (1.5%, plasma potassium concentration ϭ 4.3 mmol/L) to a low level (0.4%, plasma potassium concentration ϭ 3.9 mmol/L) increased the number of arteriosclerotic arteries in the myocardium by approximately 50%.1 More recently, we reported that elevation of dietary potassium intake reduced the severity of neointimal proliferative lesion formation in the arteries of rats and pigs after balloon angioplasty. In the study in normal adult rats, increasing potassium in the diet from a low level (0.1%) to a high level (4.0%) reduced the neointimal to medial area ratio by 46%, in association with an increase in plasma potassium concentration from 4.3 to 5.8 mmol/L. 2 In the coronary artery of pigs after balloon angioplasty, the neointimal to medial area ratio was reduced by 45% in association with an increase in dietary potassium intake from 0.25% (plasma potassium concentration ϭ 3.1 mmol/L) to 2.0% (plasma potassium concentration ϭ 4.0 mmol/L). The etiology of formation of both the arteriosclerotic lesion and the neointimal proliferative lesion associated with angioplasty have been studied extensively. 4 -7 Growth factors released at the site by platelets, endothelial cells, white blood cells, and vascular smooth muscle cells stimulate migration of vascular smooth muscle cells from the media to the subintima, where they subsequently proliferate and synthesize extracellular matrix proteins. Migration to the point of injury is directed by platelet-derived growth factor BB (PDGF-BB), 8 -11 , whereas basic fibroblast growth factor (bFGF) and PDGF-BB are the prominent regulators of vascular smooth muscle cell proliferation. 6,8,9,12,13 Transforming growth factor beta 1 (TGF-␤1) stimulates synthesis of collagen and other extracellular matrix proteins by vascular smooth muscle cells in the subintima.5,14 The mechanism of the observed inhibition of arteriosclerotic lesion formation and neointimal proliferation by elevation of potassium intake may have included effects of extracellular potassium concentration on the release of these cytokines, or on their actions on vascular smooth muscle cell proliferation and migration.In this study we analyzed the effects of changes in extracellular potassium concentration in a physiologic range on the actions of PDGF-BB, bFGF, and 5% fetal bovine serum (5% FBS) to stimulate proliferation of vascular smooth muscle cells in vitro. The responses of vascular smooth muscle cells derived from explants of pig coronary arteries to the cytokines most important in the etiology of vascular lesions were assessed in media with potassium concentrations ranging from 3 to 6 mmol/L. Both DNA synthesis and cell proliferation were analyzed during changes in potassium concentration lasting from 1 to 7 days. MATERIALS AND METHODS Vascular Smooth Muscle Cell Isolation and CultureVascular smooth muscle cells were obtained from microdissected explants of the left circumflex coronary artery of castrated male,...

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Section: Effect Of Potassium Concentration On Vascularmentioning

confidence: 72%

Section: Effect Of Potassium Concentration On Vascularmentioning

confidence: 99%

Section: Dna Synthesismentioning

confidence: 99%

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Increased potassium concentration inhibits stimulation of vascular smooth muscle proliferation by PDGF-BB and bFGF

Mamaril

Young

2000

American Journal of Hypertension

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“…24 The inhibitory effect of potassium on migration together with an effect on proliferation may account for the large magnitude of reduction in neointima formation associated with a high dietary intake of potassium observed in the angioplasty studies in rats and pigs. 1,2 Figure 2. Effect of 3-to 4-week exposure to changes in potassium concentration on vascular smooth muscle cell migration (20 ng/mL PDGF-BB) in vitro (potassium effect PϽ0.001, 2-way ANOVA, PDGF-BB effect PϽ0.001, 2-way ANOVA).…”

Section: Discussionmentioning

confidence: 99%

“…1,2 In experiments with rats and pigs, animals fed a high-potassium diet had significantly less neointimal area at the site of injury than animals fed a normal-or low-potassium diet. The cause of the neointimal proliferative lesion that occurs after angioplasty has been studied extensively by others and is known to include several alterations in the function of cells of the arterial wall.…”

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confidence: 99%

Inhibition of Vascular Smooth Muscle Cell Migration by Elevation of Extracellular Potassium Concentration

Mason²,

Young³

2000

Hypertension

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Abstract-The effect of potassium on the migration of vascular smooth muscle cells was analyzed in media made with extracellular potassium concentrations of 3, 4, 5, and 6 mmol/L. The migration of cultured porcine coronary artery cells was stimulated with platelet-derived growth factor (PDGF)-BB. In the first study, cells were exposed to PDGF-BB at concentrations of 0, 10, or 20 ng/mL for 5 hours with the use of a Boyden chamber. Cells were quiescent overnight in 0.5% fetal bovine serum in Dulbecco's modified Eagle's medium with an extracellular potassium concentration of 4 mmol/L. With increasing potassium concentration, migration was significantly inhibited (PϽ0.02, 2-way ANOVA).In the cells exposed to 10 ng/mL PDGF-BB, migration ranged from 500Ϯ86% to 294Ϯ44% (value in wells with 0 ng/mL PDGF-BB and 4 mmol/L potassium concentrationϭ100%) in medium containing 3 to 6 mmol/L extracellular potassium concentration (PϽ0.03). Long-term potassium exposure was investigated in cells grown in 5% serum in Dulbecco's modified Eagle's medium with an extracellular potassium concentration of 3, 4, 5, or 6 mmol/L for 3 to 4 weeks. Migration was assessed with 0 or 20 ng/mL PDGF-BB. Migration was significantly inhibited by the elevation of extracellular potassium concentration (PϽ0.01, 2-way ANOVA). With 20 ng/mL PDGF-BB, the migration rates ranged from 152Ϯ11% in medium with 3 mmol/L potassium to 69Ϯ5% in 6 mmol/L potassium (PϽ0.01). Increases in extracellular potassium concentration within the physiological range significantly and directly inhibit vascular smooth muscle cell migration. Key Words: arteries Ⅲ atherosclerosis Ⅲ neointima Ⅲ platelet-derived growth factor I n recent studies in this laboratory, an inverse relationship was observed between dietary potassium content and the severity of neointimal proliferation after balloon angioplasty. 1,2 In experiments with rats and pigs, animals fed a high-potassium diet had significantly less neointimal area at the site of injury than animals fed a normal-or low-potassium diet. The cause of the neointimal proliferative lesion that occurs after angioplasty has been studied extensively by others and is known to include several alterations in the function of cells of the arterial wall. Of significant importance are the migration from the media to the subintima and the subsequent proliferation of medial vascular smooth muscle cells. During migration to the intima, the cells change from the differentiated, contractile phenotype to the dedifferentiated, synthetic state that is associated with proliferation. [3][4][5][6] Platelet-derived growth factor (PDGF) is a potent chemoattractant and mitogen for cells of mesenchymal origin and for vascular smooth muscle cells. [7][8][9][10] Previously, results from experiments in our laboratory have been consistent with the hypothesis that elevated extracellular potassium concentration inhibits the functions of platelets and vascular smooth muscle cells, including proliferation, 11,12 believed to be involved in neointimal proliferative lesion form...

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Inhibition of restenosis lesion formation in the swine coronary artery by dietary potassium

Cited by 2 publications

References 0 publications

Increased potassium concentration inhibits stimulation of vascular smooth muscle proliferation by PDGF-BB and bFGF

Increased potassium concentration inhibits stimulation of vascular smooth muscle proliferation by PDGF-BB and bFGF

Inhibition of Vascular Smooth Muscle Cell Migration by Elevation of Extracellular Potassium Concentration

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