Abstract:
BACKGROUND:G protein-linked receptors are involved in the processes that lead to intimal hyperplasia. This study examined the role of Galphaq signaling pathways in vascular smooth muscle cell (SMC) proliferation in vitro. METHODS:Rat pulmonary artery SMCs were cultured in vitro. Standard assays of cellular DNA synthesis, proliferation, phospholipase C-beta (PLCbeta) activation, and extracellular signal-regulated kinase (ERK1/2) phosphorylation were used to study the response to angiotensin II (a specific Galphaq agonist; 0.1-100 micromol/L) in the presence and absence of GP-2A (a competitive Galphaq inhibitor; 10 micromol/L) and the PLCbeta inhibitor U73122 (10micromol/L). RESULTS:Angiotensin II induced SMC DNA synthesis and cell proliferation. DNA synthesis was inhibited by both Galphaq inhibitor, GP-2A, and PLCbeta inhibitor U73122, in a dose-dependent manner (66% +/- 7% of angiotensin II alone at 10 micromol/L for GP-2A [P <.05] and 63% +/- 6% for U73122). GP-2A completely inhibited angiotensin II-induced Galphaq-mediated PLCbeta phosphorylation. Activation of ERK1/2 by angiotensin II was significantly reduced by GP-2A (P <.05) and by PLCbeta inhibition (P <.05). CONCLUSION:Inhibition of Galphaq decreases PLCbeta and ERK1/2 phosphorylation, leading to decreased SMC proliferation in vitro. Understanding specific signal transduction pathways will be an integral component of anti-restenosis therapy.Clinical Relevance The universal response of a blood vessel to injury is chronic wound healing, which includes the development of intimal hyperplasia and subsequent remodeling of the vessel wall. This can lead to luminal narrowing in as many as 30% of patients undergoing angioplasty. Neointimal formation is the principal cause of in-stent recurrent stenosis. Intimal hyperplasia is in part produced by smooth muscle cell (SMC) proliferation. Understanding the keys to the proliferation of SMCs will enable therapies to be developed that may inhibit the initial development of intimal hyperplasia. Whereas in the past many studies focused on the multiple mechanical, humoral, and cellular elements that induce SMC proliferation, molecular therapeutics focuses on key choke points within the cell that can be used to inhibit proliferation. One of these key choke points is signal transduction. Galphaq is one of the ubiquitous signal transduction proteins on the membrane of SMCs. Inhibiting G proteins, such as Galphaq, would enable interference with a significant amount of the mechanical, humeral, and cellular elements that produce SMC proliferation, and thus decrease the development of intimal hyperplasia. The present study identifies and begins to map out the role of Galphaq in SMC proliferation and investigates the possible use of a small peptide in its inhibition. Other data suggest that inhibition of other G proteins will also decrease intimal hyperplasia. This is therefore a fertile area for the development of therapeutics to inhibit intimal hyperplasia. The direct relevance to the clinician is that this study identifies a transduction pathway that may be inhibited, and points in the direction of a possible molecular therapeutic target that would be beneficial as an adjunct to angioplasty or as part of a drug-eluding stent regimen.
journal_name
J Vasc Surgjournal_title
Journal of vascular surgeryauthors
Tanski WJ,Roztocil E,Hemady EA,Williams JA,Davies MGdoi
10.1016/j.jvs.2003.10.052subject
Has Abstractpub_date
2004-03-01 00:00:00pages
639-44issue
3eissn
0741-5214issn
1097-6809pii
S0741521403015908journal_volume
39pub_type
杂志文章abstract:OBJECTIVE:The optimal role for bare metal stents (BMS) or stent grafts (SG) in femoropopliteal occlusive disease (FPOD) is as of yet undefined. Understanding the clinical consequences of failure can help guide initial treatment decisions. The goal of this study was to define the nature, frequency, and risk factors for ...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2013.05.094
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND:In the era of rising endovascular treatment of thoracoabdominal aortic aneurysms (TAAAs), the analysis of visceral vessel (VV) patency after open surgical repair is crucial to provide a future benchmark between these different approaches. This study reports the late outcomes of a single-center experience wit...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2017.08.067
更新日期:2018-04-01 00:00:00
abstract:BACKGROUND:The sandwich technique is an endovascular off-the-shelf solution for patients with thoracoabdominal aortic aneurysms (TAAAs). In a sandwich configuration, the chimney stent runs in the middle of a space created by two or three aortic endografts. METHODS:All patients with TAAAs who were treated with the sand...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2013.12.044
更新日期:2014-06-01 00:00:00
abstract:OBJECTIVE:This study was conducted to investigate factors influencing the outcome of all open operations for aortoiliofemoral (AIF) revascularization performed by a single surgeon at a tertiary referral center. METHODS:The series included 355 direct reconstructions and 181 extra-anatomic bypass (EAB) grafts in 339 men...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2006.09.065
更新日期:2007-03-01 00:00:00
abstract::Surgical management of major venous injuries remains controversial. The medical records of 184 patients with major venous injury were reviewed. Forty-three patients had isolated venous injury; 31 of 43 patients (72%) underwent ligation to treat their vein injury. Another 141 patients had combined arterial and venous i...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:
更新日期:1986-12-01 00:00:00
abstract:PURPOSE:The increasing demand for venous duplex scans despite the relative rarity of detecting acute deep venous thrombosis (DVT) prompted us to review our experience with this diagnostic method. METHODS:We retrospectively analyzed the results and indications of 2993 lower extremity venous duplex scans performed betwe...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/s0741-5214(96)70251-3
更新日期:1996-05-01 00:00:00
abstract:OBJECTIVE:Many factors impair healing of chronic venous ulcer (CVU), and many theories have been proposed to explain their pathogenesis. Coagulation factor XIII (FXIII) influences tissue regeneration and angiogenesis with effects on wound healing. Because FXIII properties depend upon its genetic variants, we investigat...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2006.06.006
更新日期:2006-10-01 00:00:00
abstract:OBJECTIVES:To assess outcomes and develop duplex scan criteria that will reliably determine the luminal status of covered and uncovered renal stents following fenestrated and branched endovascular repair. METHODS:A prospective database of patients treated with fenestrated and branched endografts between 2001 and 2006 ...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2008.11.024
更新日期:2009-04-01 00:00:00
abstract:OBJECTIVE:Inflammatory modulators are important in the pathogenesis of aneurysmal disease. Gene expression profiling of experimental abdominal aortic aneurysm (AAA) tissue demonstrated upregulation of the FK506BP12 (rapamycin binding protein) gene product. Rapamycin is a potent immunosuppressor that prevents recurrent ...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2004.05.020
更新日期:2004-08-01 00:00:00
abstract:OBJECTIVES:P-selectin inhibition has been found to limit venous thrombosis. We hypothesize that elevated levels of P-selectin will amplify thrombosis, mediated by procoagulant microparticles (MPs). METHODS:Male mice (Mus musculus, n659), 20 to 25 grams, underwent IVC ligation to induce thrombosis. Groups consisted of ...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/s0741-5214(03)01033-4
更新日期:2003-11-01 00:00:00
abstract:OBJECTIVE:To describe our experience with endoluminal stent graft repair of aortobronchial fistulas. METHODS:We reviewed the records of patients treated with endoluminal stent grafting of aortobronchial fistulas at a private teaching hospital. All patients underwent the following diagnostic studies: computed tomograph...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1067/mva.2002.118583
更新日期:2002-02-01 00:00:00
abstract:BACKGROUND:The neoaortoiliac system (NAIS) has gained popularity as a durable procedure for treating aortic graft infections. However, one of the disadvantages has been a long operation that can take up to 10 hours. The goal of this study was to assess the feasibility of staging the NAIS procedure with deep vein harves...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2008.06.067
更新日期:2008-11-01 00:00:00
abstract:PURPOSE:To evaluate the patency and hemodynamic impact of a cryopreserved allograft venous valve transplanted to the superficial femoral vein (SFV) of a canine insufficiency model aided by a distal arteriovenous fistula (dAVF). METHODS:Eight greyhounds had intravenous hemodynamic parameters measured (venous filling ti...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/s0741-5214(97)70095-8
更新日期:1997-11-01 00:00:00
abstract:BACKGROUND:Long-term (tunneled cuffed) hemodialysis catheters are frequently used vascular access in renal failure patients. Catheter-related bloodstream infection (CRBSI) is a common complication of long-term hemodialysis catheters, with severe morbidities and high risk of mortality. Management of CRBSI by systemic an...
journal_title:Journal of vascular surgery
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jvs.2017.05.119
更新日期:2017-11-01 00:00:00
abstract::Patent false lumen after endovascular stent graft treatment of type B aortic dissection is a predictor for late death and retreatment. Between June 2008 and March 2010, five men with patent false lumen, due to a type B dissection previously treated with thoracic stent graft, underwent endovascular coiling treatment. W...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2010.11.110
更新日期:2011-07-01 00:00:00
abstract:OBJECTIVE:Arteriovenous fistula (AVF) is the preferred access for hemodialysis. Percutaneous transluminal angioplasty(PTA) has become a choice for AVF stenosis and ultrasound has been used in PTA more frequently. METHODS:This single-center retrospective cohort study analyzed 129 patients who underwent PTA in the First...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2020.11.041
更新日期:2020-12-16 00:00:00
abstract::Dr F. Inest practices surgery at a renowned medical center but is concerned because increasing numbers of medical insurers are excluding his institution from coverage. Many of his former referring physicians are beginning to send their patients elsewhere for this reason. The marketing people have been busy increasing ...
journal_title:Journal of vascular surgery
pub_type: 社论
doi:10.1016/j.jvs.2016.02.001
更新日期:2016-04-01 00:00:00
abstract:OBJECTIVE:Increased vascularization is considered an important contributing factor for plaque vulnerability. Microvascular proliferative disease in patients with diabetes results in renal damage and visual loss. We assessed the hypothesis that vascularization in carotid atherosclerotic tissue is increased in diabetic p...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2011.04.061
更新日期:2011-11-01 00:00:00
abstract:PURPOSE:The purpose of this study was the report of the results of a consecutive series of carotid endarterectomy (CEA), performed by one surgeon and independently assessed by a neurologist, in which the achievability of selective early control of the distal internal carotid artery (ICA) was prospectively recorded. ME...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1067/mva.2002.122028
更新日期:2002-07-01 00:00:00
abstract::In an attempt to assess the efficacy of thrombolytic infusions for arterial ischemia, a questionnaire was distributed to 142 vascular surgeons. Data from 45 respondents who had experience with thrombolytic infusion in 623 patients were reviewed. A successful outcome was obtained in 313 of 623 patients (50.2%). Morbidi...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1067/mva.1987.avs0060045
更新日期:1987-07-01 00:00:00
abstract::Fistulous communication between the aorta and esophagus is a rare but usually fatal disorder. Esophageal foreign bodies have been reported to cause aortoesophageal fistula rarely. Spontaneous aortoesophageal fistula as a result of atherosclerotic disease of the aorta has not been reported. This article describes a cas...
journal_title:Journal of vascular surgery
pub_type: 杂志文章,评审
doi:10.1067/mva.1987.avs0060379
更新日期:1987-10-01 00:00:00
abstract::Surgical repair of proximal right subclavian artery aneurysms can be difficult. They typically require a combined mediastinal exposure to control the innominate and right common carotid arteries and a supra- or infraclavicular exposure for distal control, with either a segmental resection and bypass or a bifurcated re...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2010.07.050
更新日期:2011-02-01 00:00:00
abstract::Intra-aortic inferior vena cava filter placement is a rare event. We describe a case in which a permanent vena caval filter was retrieved from the aorta with endovascular techniques. Knowledge of filter design, catheters, and available wires is important to perform this procedure safely. ...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2011.05.090
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:We undertook this study to assess the outcome of spontaneous dissection of the renal artery and its branches surgically treated with extracorporeal reconstruction and autotransplantation. SUBJECTS:Between 1975 and 1996, 15 consecutive patients (19 kidneys) with spontaneous renal artery dissection underwent ren...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/s0741-5214(02)75453-0
更新日期:2003-07-01 00:00:00
abstract:OBJECTIVE:The objective of this study was to assess the reduction in quality of life (QoL) caused by the persistence of primary plantar hyperhidrosis (PPH) symptoms and the level of satisfaction in PPH patients after retroperitoneoscopic lumbar sympathectomy (RLS). The efficacy, safety, and procedure of bilateral RLS i...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2017.05.126
更新日期:2017-12-01 00:00:00
abstract:OBJECTIVE:Abdominal aortic aneurysms (AAAs) are associated with generalized arterial dilation, torturosity, and altered matrix composition, which suggests a generalized systemic weakness throughout the entire vasculature. The aim of this study was to determine whether this phenomenon was present in the venous tissue of...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1067/mva.2002.122877
更新日期:2002-05-01 00:00:00
abstract:OBJECTIVE:This study reviews the results of en bloc resection of the inferior vena cava (IVC) for malignant tumor excision and reconstruction. METHODS:A prospective database was reviewed. IVC resection was categorized as suprarenal, perirenal, infrarenal, or extensive (>one segment resected). Repairs were divided into...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2011.11.054
更新日期:2012-05-01 00:00:00
abstract:OBJECTIVE:During endovascular aneurysm repair (EVAR), severely tortuous aortoiliac anatomy can alter the deployment and conformability of the endograft. The accuracy of treatment length measurements is commonly recognized to be affected by severe tortuosity. However, the exact mechanism of the postintervention length d...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.jvs.2016.09.041
更新日期:2017-05-01 00:00:00
abstract:OBJECTIVE:Deep venous arterialization (DVA) is a technique aimed at providing an option for chronic limb-threatening ischemia patients with no options except amputation. In patients with no outflow distal targets permitting bypass, DVA involves creating a connection between a proximal arterial inflow and a distal venou...
journal_title:Journal of vascular surgery
pub_type: 杂志文章,评审
doi:10.1016/j.jvs.2019.10.085
更新日期:2020-06-01 00:00:00
abstract:PURPOSE:The antiproliferative and antisecretory effects of somatostatin have many potential uses in the clinical setting. Retroviral gene transfer of somatostatin to endothelium is a potential means of local delivery of this peptide to specific vascular beds. This investigation was designed to determine whether transdu...
journal_title:Journal of vascular surgery
pub_type: 杂志文章
doi:10.1016/s0741-5214(98)70278-2
更新日期:1998-05-01 00:00:00