Involvement of furin-like proprotein convertases in the arterial response to injury

Sluijter, Joost P.G.; Verloop, Robert E.; Pulskens, Wilco P.; Velema, Evelyn; Grimbergen, Jos; Quax, Paul H.A.; Goumans, Marie–José; Pasterkamp, Gérard; Kleijn, Dominique P.V. de

doi:10.1016/j.cardiores.2005.05.016

Cited by 29 publications

(27 citation statements)

References 28 publications

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“…Sluijter et al [28] demonstrated in a recent study that furin-like protein convertases, proteolytic activators of proproteins, are involved in the vessel response to injury, possibly through activation of the TGF-β-Smad signaling pathway, and identified these activators as possible targets to inhibit intimal hyperplasia. Other studies also centered on protein convertases have indicated that these enzymes play an essential role in vascular diseases owing to their involvement in vascular injury via effects on growth factors and mediators [29].…”

Section: Discussionmentioning

confidence: 99%

TGF-β<sub>1</sub> Upregulation in the Aging Varicose Vein

Pascual¹,

Mendieta²,

García‐Honduvilla

et al. 2007

J Vasc Res

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Background: Although the etiology of venous insufficiency is not well understood, immune response and aging are beginning to emerge as contributing factors. Factors involved in tissue remodeling such as TGF-β₁ also seem to play an important role in extracellular matrix production. The aim of this study was to explore the relationship between chronic venous insufficiency and TGF-β₁ examining the latent/mature form of TGF-β₁ and the presence of mast cells. Effects of age were also evaluated. Methods: Saphenous veins were obtained from patients subjected to aortocoronary bypass (controls) and undergoing varicose vein surgery. These were immunolabeled using anti-LAP TGF-β₁/anti-TGF-β₁ antibodies and subjected to Western blot. Mast cell population was identified by metachromatic staining.Results:Latent TGF-β₁ was significantly reduced in varicose veins from older subjects. In contrast, smooth muscle cells obtained from the varicosities showed intense levels. Mature TGF-β₁ significantly differed between healthy and varicose veins. No mature TGF-β₁ was detected in the cell cultures. Mast cell number and degranulation were increased with aging and varicose disease, colocalizing with the mature form of TGF-β₁. Conclusion: Aging and varicose pathology induce dysregulation of TGF-β₁ that could play an important role in the fibrous process, representing the final stages of venous insufficiency.

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Section: Discussionmentioning

confidence: 99%

TGF-β<sub>1</sub> Upregulation in the Aging Varicose Vein

Pascual¹,

Mendieta²,

García‐Honduvilla

et al. 2007

J Vasc Res

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“…In adventitial and intimal areas of arteries, the levels of phosphorylated Smad 1/5 and 2/3, MT1-MMP, MMP-2 and furin are increased after balloon dilation. Moreover, furin inhibition can reduce the intimal and adventitial areas, suggesting that furin is involved in neointima formation [84]. The TGF-b-Alk5-Smad2/3 or TGF-b-Alk1-Smad1/5 pathway, which is activated by balloon dilation stimulus, can stimulate collagen production, cell proliferation and migration, and MMP production [85].…”

Section: Furin Promotes Cell Proliferation and Ecm Synthesis By Activmentioning

confidence: 99%

Proprotein convertase furin/PCSK3 and atherosclerosis: New insights and potential therapeutic targets

2017

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“…In the vessel wall, inactive TGF-␤ can be activated via the cooperation between the mannose-6-phosphate/insulin-like growth factor II receptor and the urokinase-type plasminogen activator receptor, plasmin, thrombospondin, and furin-like proprotein convertases; the latter are responsible for TGF-␤ activation after arterial injury. 1 In contrast, BMPs are secreted in an active form and regulated through reversible interactions with extracellular antagonists, including noggin, chordin, and DAN. 2 These interactions determine the bioavailability of different TGF-␤s/BMPs for binding to their receptors.…”

Section: Tgf-␤ Superfamily Members and Effects On Vascular Cellsmentioning

confidence: 99%

Transforming Growth Factor-βs and Vascular Disorders

Bobik

2006

ATVB

239

186

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Abstract-Transforming growth factor-␤ (TGF-␤) superfamily members, TGF-␤ and bone morphogenetic proteins (BMPs), are potent regulatory cytokines with diverse functions on vascular cells. They signal through heteromeric type I and II receptor complexes activating Smad-dependent and Smad-independent signals, which regulate proliferation, differentiation, and survival. They are potent regulators of vascular development and vessel remodeling and play key roles in atherosclerosis and restenosis, regulating endothelial, smooth muscle cell, macrophage, T cell, and probably vascular calcifying cell responses. In atherosclerosis, TGF-␤ regulates lesion phenotype by controlling T-cell responses and stimulating smooth muscle cells to produce collagen. It contributes to restenosis by augmenting neointimal cell proliferation and collagen accumulation. Defective TGF-␤ signaling in endothelial cells attributable to mutations in endoglin or the type I receptor ALK-1 leads to hereditary hemorrhagic telangiectasia, whereas defective BMP signaling attributable to mutations in the BMP receptor II has been associated with development of primary pulmonary hypertension. The development of mouse models with either cell type-specific or general inactivation of TGF-␤/BMP signaling has started to reveal the importance of the regulatory network of TGF-␤/BMP pathways in vivo and their significance for atherosclerosis, hereditary hemorrhagic telangiectasia, and primary pulmonary hypertension. This review highlights recent findings that have advanced our understanding of the roles of TGF-␤ superfamily members in regulating vascular cell responses and provides likely avenues for future research that may lead to novel pharmacological therapies for the treatment or prevention of vascular disorders.

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Involvement of furin-like proprotein convertases in the arterial response to injury

Abstract: This study demonstrates that furin-like PCs are involved in the arterial response to injury possibly through activation of the TGF-beta-Smad signaling pathway and identifies furin-like PCs as a possible target to inhibit intimal hyperplasia.

Cited by 29 publications

References 28 publications

TGF-β<sub>1</sub> Upregulation in the Aging Varicose Vein

TGF-β<sub>1</sub> Upregulation in the Aging Varicose Vein

Proprotein convertase furin/PCSK3 and atherosclerosis: New insights and potential therapeutic targets

Transforming Growth Factor-βs and Vascular Disorders

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