Towards the prevention of vein graft failure

Mehta, Dheeraj; Izzat, Mohammad Bashar; Bryan, Alan J.; Angelini, Gianni D

doi:10.1016/s0167-5273(97)00214-3

Cited by 76 publications

(59 citation statements)

References 43 publications

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“…93 Both processes are characterized by an increased cell proliferation in adventitia, apoptosis and necrosis of medial VSMCs, adventitial thickening, fibroblast-to-myofibroblast conversion, directional migration of activated adventitial cells to the neointima, and vascular remodeling. 11,12,[93][94][95][96][97][98] In the transplant there is a transient acute inflammation, platelet adhesion, and release of vasoactive substances, cytokines, and growth factors. 95 In an elegant work, Shi et al 94 demonstrated that, after porcine autologous vein-to-artery grafting, SM ␣-actin ϩ , BrdU ϩ pulse-labeled adventitial fibroblasts from adjacent tissue translocate from the interposed vein segment and, with time, migrate to the subendothelial space where numerous SM ␣-actin ϩ , BrdU ϩ -labeled myofibroblasts accumulate.…”

Section: Adventitia Response In Autologous Vein-to-artery Graft and Tamentioning

confidence: 99%

Contribution of Adventitial Fibroblasts to Neointima Formation and Vascular Remodeling

Sartore

Chiavegato

Faggin

et al. 2001

Circulation Research

453

376

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Abstract-The adventitial layer surrounding the blood vessels has long been exclusively considered a supporting tissue the main function of which is to provide adequate nourishment to the muscle layers of tunica media. Although functionally interconnected, the adventitial and medial layers are structurally interfaced at the external elastic lamina level, clearly distinguishable at the maturational phase of vascular morphogenesis. Over the last few years the "passive" role that the adventitia seemed to play in experimental and spontaneous vascular pathologies involving proliferation, migration, differentiation, and apoptosis of vascular smooth muscle cells (VSMCs) has been questioned. It has been demonstrated that fibroblasts from the adventitia display an important partnership with the resident medial VSMCs in terms of phenotypic conversion, proliferation, apoptotic, and migratory properties the result of which is neointima formation and vascular remodeling. This article is an attempt at reviewing the major themes and more recent findings dealing with the phenotypic conversion process that leads adventitial "passive" (static) fibroblasts to become "activated" (mobile) myofibroblasts. This event shows some facets in common with vascular morphogenesis, ie, the process of recruitment, incorporation, and phenotypic conversion of cells surrounding the primitive endothelial tube in the definitive vessel wall. We hypothesize that during the response to vascular injuries in the adult, "activation" of adventitial fibroblasts is, at least in part, reminiscent of a developmental program that also invests, although with distinct spatiotemporal features, medial VSMCs.

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Section: Adventitia Response In Autologous Vein-to-artery Graft and Tamentioning

confidence: 99%

Contribution of Adventitial Fibroblasts to Neointima Formation and Vascular Remodeling

Sartore

Chiavegato

Faggin

et al. 2001

Circulation Research

453

376

View full text Add to dashboard Cite

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“…Unfortunately, pathological intimal hyperplasia (IH) ensues after these procedures largely due to the proliferation of vascular smooth muscle cells (VSMCs) in the media and their migration into the intima of the treated vessel (1)(2)(3). Such proliferation is induced by a number of growth-stimulatory signals that are activated by vascular injury and leads to high long-term failure rates of bypass surgery and angioplasty for treatment of cardiovascular disease (4)(5)(6)(7)(8)(9)(10)(11)(12). These failures often cause death and disability and may require repeated treatment by surgery or angioplasty.…”

mentioning

confidence: 99%

Distinct roles of E2F proteins in vascular smooth muscle cell proliferation and intimal hyperplasia

Giangrande

Zhang

Tanner

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Intimal hyperplasia (IH) and restenosis limit the long-term utility of bypass surgery and angioplasty due to pathological proliferation and migration of vascular smooth muscle cells (VSMCs) into the intima of treated vessels. Consequently, much attention has been focused on developing inhibitory agents that reduce this pathogenic process. The E2F transcription factors are key cell cycle regulators that play important roles in modulating cell proliferation and cell fate. Nonselective E2F inhibitors have thus been extensively evaluated for this purpose. Surprisingly, these E2F inhibitors have failed to reduce IH. These findings prompted us to evaluate the roles of different E2Fs during IH to determine how selective targeting of E2F isoforms impacts VSMC proliferation. Importantly, we show that E2F3 promotes proliferation of VSMCs leading to increased IH, whereas E2F4 inhibits this pathological response. Furthermore, we use RNA probes to show that selective inhibition of E2F3, not global inhibition of E2F activity, significantly reduces VSMC proliferation and limits IH in murine bypass grafts.cell cycle ͉ RNA therapeutics C ardiovascular disease is the leading cause of death in developed countries and claims almost 40% of all deaths in the United States. Coronary bypass surgery and angioplasty are two major therapeutic modalities for treating cardiovascular disease. Unfortunately, pathological intimal hyperplasia (IH) ensues after these procedures largely due to the proliferation of vascular smooth muscle cells (VSMCs) in the media and their migration into the intima of the treated vessel (1-3). Such proliferation is induced by a number of growth-stimulatory signals that are activated by vascular injury and leads to high long-term failure rates of bypass surgery and angioplasty for treatment of cardiovascular disease (4-12). These failures often cause death and disability and may require repeated treatment by surgery or angioplasty. Accordingly, development of molecular strategies that effectively inhibit such pathogenic cellular processes has been the focus of much research and many clinical trials over the past 20 years (13).E2F is a family of structurally related DNA binding proteins whose activity is regulated by the retinoblastoma tumor suppressor protein Rb and its related family members, p107 and p130 (14). In mammalian cells, at least eight members of the E2F family of proteins exist, and these proteins possess both distinct and overlapping roles in proliferation, apoptosis, and development (15-21). In general, the mammalian E2F family can be divided into subclasses based upon shared functional properties and sequence homologies. For instance, E2F1, E2F2, and E2F3 are strong transcriptional activators whose accumulation is tightly regulated and in most cell types correlates with increased cell proliferation (22,23). In contrast, E2F4 and E2F5 are not regulated by cell growth and are involved in the repression of growth-promoting E2F responsive genes (24). Given that E2F proteins are key regulators of the ce...

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“…Injury-induced neointimal hyperplasia develops through a complex process including platelet aggregation, leukocyte chemotaxis, VSMC proliferation and migration, extracellular matrix (ECM) changes, and endothelial cell proliferation. [13][14][15] In order to improve vascular damage, effective potential treatments on these mechanisms, which play a role in the pathophysiology of neointimal hyperplasia, have been investigated.…”

Section: Discussionmentioning

confidence: 99%

Effect of Tadalafil on Neointimal Hyperplasia in a Rabbit Carotid Artery Anastomosis Model

Guzeloglu

Aykut

Albayrak

et al. 2013

ATCS

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Purpose: Intimal thickening, which results from the response to arterial damage caused by therapeutic interventions or other reasons, is usually called as neointima. Neointimal hyperplasia is a main step in the pathogenesis of late-term restenosis, which is developed after vascular interventions. Reduction in nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling plays a substantial role in the pathogenesis of neointima formation. Phosphodiesterase V is detected in the peripheral coronary and pulmonary vascular smooth muscle cells and in the cardiac tissue. Based on the effects of phosphodiesterase V inhibitors on vascular smooth muscle cells, in the present study, the effect of tadalafil, a new member of phosphodiesterase V inhibitors, on neointimal hyperplasia was investigated in the rabbit carotid artery anastomosis model. Materials and Methods: Fourteen male New Zealand white rabbits weighing between 2.5-3 kg, were used. The rabbits were randomly divided into two equal groups; tadalafil group received oral tadalafil (2 mg/kg/day), and PBS group received sterile PBS solution (normal saline; 2 mg/kg/day) for 28 days after the surgery. The right carotid arteries of all rabbits were anastomosed in an end-to-end fashion using 8/0 polypropylene suture. The rabbits were sacrificed at the end of the postoperative period of 28 days. After sacrificing, firstly anastomosis segment on the right carotid artery and secondly a part of the left carotid artery (as control) of each rabbit were removed. Morphometric examination of tissue sections was performed under a light microscope connected to an image capture system. Results: There was a significant difference between the right and left carotid arteries in terms of intimal area and intima/media ratio both in tadalafil and PBS groups (p <0.001 for each). Intimal area and intima/media ratio were increased in the right carotid arteries compared to the left carotid arteries (p <0.001 for each). Besides, when the right carotid arteries of both groups were compared using covariance analysis, it was observed that intimal area and intima/media ratio in the anastomosis site were significantly reduced with tadalafil treatment (p <0.001). Conclusion: The present study was promising in terms of tadalafil use as a new agent for the prevention of neointimal hyperplasia, which is the leading cause of late-term graft failure in vascular surgery.

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Towards the prevention of vein graft failure

Cited by 76 publications

References 43 publications

Contribution of Adventitial Fibroblasts to Neointima Formation and Vascular Remodeling

Contribution of Adventitial Fibroblasts to Neointima Formation and Vascular Remodeling

Distinct roles of E2F proteins in vascular smooth muscle cell proliferation and intimal hyperplasia

Effect of Tadalafil on Neointimal Hyperplasia in a Rabbit Carotid Artery Anastomosis Model

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