Intimal Hyperplasia and Expression of Transforming Growth Factor-β1 in Saphenous Veins and Internal Mammary Arteries Before Coronary Artery Surgery

Friedl, Reinhard; Li, Jun; Schumacher, B.; Hanke, Hartmut; Waltenberger, Johannes; Hannekum, A; Stracke, Sylvia

doi:10.1016/j.athoracsur.2004.02.066

Cited by 38 publications

(36 citation statements)

References 27 publications

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“…35 PDGF and TGF-␤1 are considered key mediators during medial and intimal thickening of autologous vein grafts 36 and have been shown to be upregulated in stenotic vein grafts. 6,24 PDGF-BB strongly induced HAS2 mRNA and HA synthesis in venous SMC, as has been shown before in arterial SMC 15 and mesothelial 13 cells. TGF-␤1 slightly reduces HAS2 expression in mesothelial cells 13 and induces HAS2 in corneal endothelial cells.…”

Section: Van Den Boom Et Al Hyaluronic Acid In Human Saphenous Vein Gsupporting

confidence: 54%

“…All native veins showed intimal thickening, which is in line with previous reports of pronounced intimal thickening of primary vein graft tissue. 6,24 Strong accumulation of HA in association with SMC was observed in the thickened intima of primary as well as in arterialized saphenous vein segments. Because extracellular HA has a relatively short half-life, 25 the presence of HA in arterialized SVG suggests that HA synthesis is induced after bypass grafting.…”

Section: Discussionmentioning

confidence: 98%

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Differential Regulation of Hyaluronic Acid Synthase Isoforms in Human Saphenous Vein Smooth Muscle Cells

Boom

Sarbia

Lipinski

et al. 2006

Circulation Research

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Abstract-Autologous saphenous vein bypass grafts (SVG) are frequently compromised by neointimal thickening and subsequent atherosclerosis eventually leading to graft failure. Hyaluronic acid (HA) generated by smooth muscle cells (SMC) is thought to augment the progression of atherosclerosis. The aim of the present study was (1) to investigate HA accumulation in native and explanted arterialized SVG, (2) to identify factors that regulate HA synthase (HAS) expression and HA synthesis, and (3) to study the function of the HAS2 isoform. In native SVG, expression of all 3 HAS isoforms was detected by RT-PCR. Histochemistry revealed that native and arterialized human saphenous vein segments were characterized by marked deposition of HA in association with SMC. Interestingly, in contrast to native SVG, cyclooxygenase (COX)-2 expression by SMC and macrophages was detected only in arterialized SVG. In vitro in human venous SMC HAS isoforms were found to be differentially regulated. HAS2, HAS1, and HA synthesis were strongly induced by vasodilatory prostaglandins via G s -coupled prostaglandin receptors. In addition, thrombin induced HAS2 via activation of PAR1 and interleukin 1␤ was the only factor that induced HAS3. By small interfering RNA against HAS2, it was shown that HAS2 mediated HA synthesis is critically involved in cell cycle progression through G 1 /S phase and SMC proliferation. In conclusion, the present study shows that HA-rich extracellular matrix is maintained after arterialization of vein grafts and might contribute to graft failure because of its proproliferative function in venous SMC. Furthermore, COX-2-dependent prostaglandins may play a key role in the regulation of HA synthesis in arterialized vein grafts. Key Words: hyaluronic acid Ⅲ extracellular matrix Ⅲ cyclooxygenase-2 Ⅲ vein graft stenosis A utologous saphenous vein grafts (SVG) are frequently used for bypass grafting in patients with symptomatic occlusive disease of coronary arteries or arteries of the lower extremities. Subsequently, the grafted vein segments are exposed to arterial blood pressure and shear stress, which are thought to initiate intensive remodeling, intimal thickening, in-graft thrombosis, and superimposed atherosclerosis associated with long-term failure rates of approximately 30% to 40%. 1,2 The pathophysiological mechanisms eventually resulting in graft failure include activation and dedifferentiation of vascular smooth muscle cells (SMC) from a contractile into a secretory phenotype characterized by high migratory and proliferative activity. 3 In addition, the extracellular matrix (ECM) undergoes remodeling in arterialized venous grafts. This remodeling is characterized by high ECM turnover conferred by matrix metalloproteinases 1, -2, and -9 4,5 and increased deposition of newly synthesized ECM components including collagen and proteoglycans. 6,7 ECM remodeling is thought to be required for the proliferative and migratory activation of SMC and to support intimal volume expansion. 8 Recently, hyaluronic acid (HA) has b...

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Section: Van Den Boom Et Al Hyaluronic Acid In Human Saphenous Vein Gsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 98%

Differential Regulation of Hyaluronic Acid Synthase Isoforms in Human Saphenous Vein Smooth Muscle Cells

Boom

Sarbia

Lipinski

et al. 2006

Circulation Research

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“…We have noted that intimal hyperplasia was present also in many saphenous veins at the time of harvesting. So far, only few morphological studies have noted the presence of pre-existing pathological changes in the human saphenous vein [39]. When compared to the uremic control vessels of venous origin, an increased staining intensity for IGFBP-1, -2 and -4 can be seen in the media of saphenous vein segments.…”

Section: Discussionmentioning

confidence: 95%

Over-expression of IGF-related peptides in stenoses of native arteriovenous fistulas in hemodialysis patients

Stracke

Könner

Köstlin

et al. 2007

Growth Hormone & IGF Research

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“…In particular, a latent form of TGF-b, latent TGF-b-binding protein 1, could play a role in intimal remodelling, favouring smooth cell migration, as recently described [32,33]. Furthermore, cytokines other than TGF-b might be involved in the development of intimal remodelling.…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor-β type II receptor in pulmonary arteries of patients with very severe COPD

Beghè¹,

Bazzan²,

Baraldo³

et al. 2006

Eur Respir J

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A mild-to-moderate increase in pulmonary arterial pressure is often associated with severe chronic obstructive pulmonary disease (COPD). Transforming growth factor (TGF)-b is a cytokine involved in the maintenance of integrity of vasculature. The aim of the study was to investigate whether the TGF-b pathway might be involved in the development of pulmonary hypertension associated with COPD.Surgical specimens from 14 patients undergoing lung transplantation for very severe COPD (forced expiratory volume in one second 17¡2% of the predicted value) and from seven donors were examined. The expression of TGF-b1 and TGF-b type II receptor (TGF-bRII), cell proliferation index and structural changes in pulmonary arteries were quantified immunohistochemically.In severe COPD patients, increased expression of TGF-bRII was observed in both the tunica media and intima, which was associated with a normal proliferation index in both layers. Conversely, significant thickening of the tunica intima, which was not present in the tunica media, was observed, suggesting that mechanisms other than cell proliferation may be involved in intimal thickening.In conclusion, in the pulmonary arteries of patients with severe chronic obstructive pulmonary disease, there is upregulation of transforming growth factor-b type II receptor expression associated with a normal proliferation index. These findings suggest the activation of an antiproliferative pathway, which might explain the relatively low degree of pulmonary hypertension observed in these subjects.

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Intimal Hyperplasia and Expression of Transforming Growth Factor-β1 in Saphenous Veins and Internal Mammary Arteries Before Coronary Artery Surgery

Cited by 38 publications

References 27 publications

Differential Regulation of Hyaluronic Acid Synthase Isoforms in Human Saphenous Vein Smooth Muscle Cells

Differential Regulation of Hyaluronic Acid Synthase Isoforms in Human Saphenous Vein Smooth Muscle Cells

Over-expression of IGF-related peptides in stenoses of native arteriovenous fistulas in hemodialysis patients

Transforming growth factor-β type II receptor in pulmonary arteries of patients with very severe COPD

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