Insulin and local growth factor PDGF induce intimal hyperplasia in bypass graft culture models of saphenous vein and internal mammary artery

Huang, Bei; Dreyer, Thomas; Heidt, Martin; Yu, Julie C.M.; Philipp, Monika; Hehrlein, F. W.; Katz, Norbert; Al-Fakhri, Nadia

doi:10.1016/s1010-7940(02)00111-2

Cited by 35 publications

(35 citation statements)

References 17 publications

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“…Since the percentage of elastic fibers remained stable during organ culture, the absolute amount of elastic fibers increased with the formation of intimal hyperplasia. This is in agreement with Huang et al who could show an increase of elastic fibers in neointimal hyperplasia of saphenous veins [19].…”

Section: Discussionsupporting

confidence: 93%

“…Local paclitaxel treatment has been shown to inhibit neointimal hyperplasia in injured rabbit carotid arteries and stented porcine coronary arteries www.elsevier.com/locate/ejcts European Journal of Cardio-thoracic Surgery 32 (2007) 906-911 § Presented at the 21st Annual Meeting of the European Association for Cardio-thoracic Surgery, Geneva, Switzerland, September [16][17][18][19]2007. [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Paclitaxel treatment reduces neointimal hyperplasia in cultured human saphenous veins☆

Schachner

Steger

Heiss

et al. 2007

European Journal of Cardio-Thoracic Surgery

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Paclitaxel treatment reduces neointimal hyperplasia in cultured human saphenous veins☆

Schachner

Steger

Heiss

et al. 2007

European Journal of Cardio-Thoracic Surgery

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“…Since FCS contains a mixture of undefined growth factors, we also assessed the effect of insulin and PDGF-BB, two key mitogens important in neointima development (18). However, in response to insulin plus PDGF, there was no difference in proliferation between the two SV-SMC populations.…”

Section: Discussionmentioning

confidence: 99%

Inherent differences in morphology, proliferation, and migration in saphenous vein smooth muscle cells cultured from nondiabetic and Type 2 diabetic patients

Madi

Riches

Warburton

et al. 2009

American Journal of Physiology-Cell Physiology

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Madi HA, Riches K, Warburton P, O'Regan DJ, Turner NA, Porter KE. Inherent differences in morphology, proliferation, and migration in saphenous vein smooth muscle cells cultured from nondiabetic and Type 2 diabetic patients. Am J Physiol Cell Physiol 297: C1307-C1317, 2009. First published September 9, 2009 doi:10.1152/ajpcell.00608.2008.-Individuals with Type 2 diabetes mellitus (T2DM) are at increased risk of saphenous vein (SV) graft stenosis following coronary artery bypass. Graft stenosis is caused by intimal hyperplasia, a pathology characterized by smooth muscle cell (SMC) proliferation and migration. We hypothesized that SV-SMC from T2DM patients were intrinsically more proliferative and migratory than those from nondiabetic individuals. SV-SMC were cultured from nondiabetic and T2DM patients. Cell morphology (light microscopy, immunocytochemistry), S100A4 expression (real-time RT-PCR, immunoblotting), proliferation (cell counting), migration (Boyden chamber assay), and cell signaling (immunoblotting with phosphorylation state-specific antibodies) were studied. SV-SMC from T2DM patients were morphologically distinct from nondiabetic patients and exhibited a predominantly rhomboid phenotype, accompanied by disrupted F-actin cytoskeleton, disorganized ␣-smooth muscle actin network, and increased focal adhesion formation. However, no differences were observed in expression of the calcium-binding protein S100A4, a marker of rhomboid SMC phenotype, between the two cell populations. T2DM cells were less proliferative in response to fetal calf serum than nondiabetic cells, but both populations had similar proliferative responses to insulin plus PDGF. Under high glucose concentration conditions in the presence of insulin, migration of diabetic SV-SMC was greater than nondiabetic cells. Glucose concentration did not affect SV-SMC proliferation. No differences in insulin or PDGF-induced phosphorylation of ERK-1/2 or components of the Akt pathway (Akt-Ser473, Akt-Thr308, and GSK-3␤) were apparent between the two populations. In conclusion, SV-SMC from T2DM patients differ from nondiabetic SV-SMC in that they exhibit a rhomboid phenotype and are more migratory, but less proliferative, in response to serum. diabetes mellitus; vein graft stenosis; metabolic memory DIABETES MELLITUS IS A SERIOUS and escalating health problem worldwide (3) that currently affects more than 2

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“…C-peptide is cleaved from proinsulin and co-secreted with insulin in response to glucose stimulation. Insulin has been reported to accelerate SMC growth and promote atherosclerosis via the activation of p44/42 MAP kinases [24][25][26][27]. The proliferation of SMCs is one of the major pathological changes in atherosclerotic lesions occurring in the diabetic state [28].…”

Section: Discussionmentioning

confidence: 99%

Human proinsulin C-peptide prevents proliferation of rat aortic smooth muscle cells cultured in high-glucose conditions

et al. 2005

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Insulin and local growth factor PDGF induce intimal hyperplasia in bypass graft culture models of saphenous vein and internal mammary artery

Abstract: These organ culture models demonstrate the effects of insulin and PDGF on intimal hyperplasia in IMA and SV representing models for arteriosclerosis and bypass graft stenosis and stressing the role of insulin and growth factors for neointima development.

Cited by 35 publications

References 17 publications

Paclitaxel treatment reduces neointimal hyperplasia in cultured human saphenous veins☆

Paclitaxel treatment reduces neointimal hyperplasia in cultured human saphenous veins☆

Inherent differences in morphology, proliferation, and migration in saphenous vein smooth muscle cells cultured from nondiabetic and Type 2 diabetic patients

Human proinsulin C-peptide prevents proliferation of rat aortic smooth muscle cells cultured in high-glucose conditions

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