Human macrophages modulate the phenotype of cultured rabbit aortic smooth muscle cells through secretion of platelet‐derived growth factor

Morisaki, Naho; Koyama, Noriyuki; Kawano, Motoharu; Mori, Seijiro; Umemiya, K; Koshikawa, Tomoko; Saitō, Yasushi; Yoshida, Sho

doi:10.1111/j.1365-2362.1992.tb01491.x

Cited by 26 publications

(13 citation statements)

References 27 publications

(11 reference statements)

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“…Interestingly, our results did not demonstrate any differences in the area fraction of α-SMA + SMCs in 2-week specimens, but did identify decreased SMC proliferation in the PGDF-KO group. The decreased proliferation in PGDF-KO mice is consistent with literature demonstrating the paracrine role of PDGF in promoting SMC migration and proliferation [10,[22][23][24][25]. One potential reason that no difference was observed in the total quantity of SMCs between the two groups is that we specifically targeted only the PDGF-B subtype.…”

Section: Myeloid Cell Pdgf-b and Tevg Neotissue Development Research Arsupporting

confidence: 75%

The Role of Myeloid Cell-Derived PDGF-B in Neotissue Formation in a Tissue-Engineered Vascular Graft

et al. 2017

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Aim: Inflammatory myeloid lineage cells mediate neotissue formation in tissueengineered vascular grafts, but the molecular mechanism is not completely understood. We examined the role of vasculogenic PDGF-B in tissue-engineered vascular graft neotissue development. Materials & methods: Myeloid cell-specific PDGF-B knockout mice (PDGF-KO) were generated using bone marrow transplantation, and scaffolds were implanted as inferior vena cava interposition grafts in either PDGF-KO or wildtype mice. Results: After 2 weeks, grafts from PDGF-KO mice had more remaining scaffold polymer and less intimal neotissue development. Increased macrophage apoptosis, decreased smooth muscle cell proliferation and decreased collagen content was also observed. Conclusion: Myeloid cell-derived PDGF contributes to vascular neotissue formation by regulating macrophage apoptosis, smooth muscle cell proliferation and extracellular matrix deposition. Progress in tissue engineering continues to promise a solution to the lack of tissue available for reconstructive and replacement surgery. Our lab has worked over the past several years developing a tissue-engineered vascular graft (TEVG) for use in congenital heart and vascular surgery. Traditionally used prosthetic materials in the form of Dacron ® or Gore-Tex ® pose significant risk for thromboembolic and infectious complications and also lack growth capacity, making them less ideal for use in the pediatric population. Our ability to create a TEVG with growth capacity [1,2] has therefore been an important advancement in the field, but graft stenosis continues to be a major limitation to widespread clinical application. We have therefore concentrated our efforts on understanding the underlying processes of TEVG neotissue formation and stenosis development.We developed a murine model of TEVG stenosis [3] and found that seeding the grafts with bone marrow-derived mononuclear cells prior to implantation increases graft patency [4] in a dose responsive manner [5], but the seeded cells disappear shortly after implantation [6,7]. We thus hypothesized that a paracrine mechanism, rather than proliferation of seeded cells, was responsible for the remodeling of the TEVG and then demonstrated that host endothelial and smooth muscle cells from the adjacent vessel migrate to form the TEVG neotissue.Host monocytes and macrophages were identified as key mediators of graft remodeling. They infiltrate the graft in large numbers shortly after implantation, and excessive infiltration leads to graft stenosis [8].

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Section: Myeloid Cell Pdgf-b and Tevg Neotissue Development Research Arsupporting

confidence: 75%

The Role of Myeloid Cell-Derived PDGF-B in Neotissue Formation in a Tissue-Engineered Vascular Graft

et al. 2017

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“…[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 formation. The purpose of the present study was to extend those results by testing the hypothesis that the elevation of extracellular potassium concentration inhibits vascular smooth muscle cell migration.…”

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confidence: 67%

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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“…44 Among the complex array of mediators taking part in atherogenesis, growth factors are capable of inducing phenotypic changes in arterial smooth muscle cells and also of increasing the synthesis of proteoglycans. 45 More important, the proteoglycans synthesized under these conditions have longer glycosaminoglycan chains.…”

Section: Discussion Some Glycosaminoglycan Species Have Greater Affinmentioning

confidence: 99%

Age-Related Changes in Populations of Aortic Glycosaminoglycans

Tovar

Cesar

Leta

et al. 1998

ATVB

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Abstract-Glycosaminoglycans were extracted from the intima and media layers of normal human thoracic aortas from donors of different ages. The arterial segments were devoid of macroscopically visible lesions obtained from patients who had no clinically evident cardiovascular disease. Total glycosaminoglycan content increases during the first 40 years of life. Changes in the content of hyaluronic acid and heparan sulfate are less noticeable. The content of chondroitin sulfate (mainly the 6-isomer) increases, whereas dermatan sulfate remains constant. Plasma LDL-affinity chromatography of dermatan sulfateϩchondroitin 4/6-sulfate fractions allowed the separation of LDL high-and low-affinity glycosaminoglycan species. Remarkably, only glycosaminoglycan species with low affinity for plasma LDL increase with age in the disease-free areas of human thoracic aortas studied. These results suggest that age-related changes in glycosaminoglycan composition of the arterial wall do not contribute to increased deposition of plasma LDL. However, the alternative explanation that individuals with arterial glycosaminoglycans that avidly bind LDL would develop early and severe cardiovascular disease and would thus be excluded from our analysis cannot be ruled out.(Arterioscler Thromb Vasc Biol. 1998;18:604-614.)Key Words: glycosaminoglycans Ⅲ chondroitin sulfate Ⅲ dermatan sulfate Ⅲ atherosclerotic risk factor Ⅲ LDL G lycosaminoglycan chains that project from proteoglycans of the arterial wall are responsible for the formation of complexes with plasma LDL. [1][2][3][4][5][6][7][8][9][10][11] This is a step in the normal exchange of components between the circulating plasma and the arterial wall. However, during atherosclerosis, this process contributes to continuous focal deposition of cholesterol-rich lipoproteins, mainly LDL, in lesions.12-14 In turn, glycosaminoglycan-LDL complexes are more easily internalized by macrophages than LDL alone, 15 thereby enhancing the formation of foam cells. Also, glycosaminoglycans induce structural alterations in LDL molecules that may potentiate their atherogenic effects.9 Therefore, the nature of the glycosaminoglycan-LDL interaction has been extensively studied. It is known that certain glycosaminoglycan species, including particular populations of a given species, have greater affinity for LDL. 6,11,16 The occurrence of atherosclerotic lesions is associated with a number of risk factors, such as elevated serum lipoprotein levels, hypertension, smoking, gender, and family history. 17 However, intrinsic factors of the arterial bed and its bloodcarrying functions also influence the occurrence of lesions. The primary evidence for this influence comes from morphological studies of necropsy material, showing that the incidence and/or severity of atherosclerotic lesions varies as a function of anatomical location. 18 -21 We have demonstrated that glycosaminoglycans from different locations vary in composition and in binding affinity for plasma LDL.11 These results suggested that glycosaminoglycan c...

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Human macrophages modulate the phenotype of cultured rabbit aortic smooth muscle cells through secretion of platelet‐derived growth factor

Cited by 26 publications

References 27 publications

The Role of Myeloid Cell-Derived PDGF-B in Neotissue Formation in a Tissue-Engineered Vascular Graft

The Role of Myeloid Cell-Derived PDGF-B in Neotissue Formation in a Tissue-Engineered Vascular Graft

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

Age-Related Changes in Populations of Aortic Glycosaminoglycans

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