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At least 19 recordsLinked to original sources
PubMed2006

ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation.

Explore the source record for details and available documents.

Adolescent↗
PubMed2003

Association of plasma homocysteine in elderly persons with atherosclerotic vascular disease and dementia, atherosclerotic vascular disease without dementia, dementia without atherosclerotic vascular disease, and no dementia or atherosclerotic vascular disease.

BACKGROUND: Increased plasma homocysteine has been associated with atherosclerotic vascular disease in elderly persons. The Framingham Study found that plasma homocysteine was a risk factor for dementia and Alzheimer's disease. METHODS: We investigated in an academic nursing home the association of plasma homocysteine with atherosclerotic vascular disease plus dementia (group 1), atherosclerotic vascular disease without dementia (group 2), dementia without atherosclerotic vascular disease (group 3), and no dementia or atherosclerotic vascular disease (group 4). RESULTS: The mean plasma homocysteine level was 15.3 +/- 3.0 micromol/L in 50 group 1 patients, 15.1 +/- 2.7 micromol/L in 50 group 2 patients, 14.4 +/- 2.7 micromol/L in 50 group 3 patients, and 10.6 +/- 3.2 micromol/L in 50 group 4 patients (p <.0001 for group 1 vs group 4, for group 2 vs group 4, and for group 3 vs group 4). CONCLUSIONS: The mean plasma homocysteine level was significantly higher in elderly patients with atherosclerotic vascular disease plus dementia, atherosclerotic vascular disease without dementia, and dementia without atherosclerotic vascular disease than in patients with no dementia or atherosclerotic vascular disease.

Aged↗
PubMed2003

Association of abnormal serum lipids in elderly persons with atherosclerotic vascular disease and dementia, atherosclerotic vascular disease without dementia, dementia without atherosclerotic vascular disease, and no dementia or atherosclerotic vascular disease.

BACKGROUND: Observational data have shown that the use of statins was associated with a lower prevalence of vascular dementia and of Alzheimer's disease. METHODS: We investigated in an academic nursing home the association of dyslipidemia with atherosclerotic vascular disease (group 1), atherosclerotic vascular disease without dementia (group 2), dementia without atherosclerotic vascular disease (group 3), and no dementia or atherosclerotic vascular disease (group 4). RESULTS: Increased serum low-density lipoprotein (LDL) cholesterol was present in 36 of 50 group 1 patients (72%), in 34 of 50 group 2 patients (68%), in 34 of 50 group 3 patients (68%), and in 18 of 50 group 4 patients (36%) (p =.0003 for 1 versus 4; p = 0.001 for 2 versus 4 and 3 versus 4). Decreased serum high-density lipoprotein (HDL) cholesterol was present in 34 of 50 group 1 patients (68%), in 35 of 50 group 2 patients (70%), in 32 of 50 group 3 patients (64%), and in 16 of 50 group 4 patients (32%) (p =.0003 for 1 versus 4; p =.0001 for 2 versus 4; p =.001 for 3 versus 4). Hypertriglyceridemia was not significantly different in the 4 groups. CONCLUSIONS: The prevalence of increased serum LDL cholesterol and decreased serum HDL cholesterol were significantly higher in elderly patients with atherosclerotic vascular disease plus dementia, atherosclerotic vascular disease without dementia, and dementia without atherosclerotic vascular disease than in patients with no dementia or atherosclerotic vascular disease.

Age Distribution↗
PubMed2006

ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation.

Explore the source record for details and available documents.

Aorta, Abdominal↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2000

Nimodipine for primary degenerative, mixed and vascular dementia.

BACKGROUND: Dementia is an age-related condition in which Alzheimer's disease (AD) and cerebrovascular disease account for the bulk of cases. The role played by calcium in regulating brain functions is well known - the calcium ion links membrane excitation to subsequent intracellular enzymatic response. Change in calcium homeostasis is one important effect of aging with repercussions on higher cortical functions. Nimodipine is an isopropyl calcium channel blocker which can easily cross the blood brain barrier. Its primary action is to reduce the number of open channels, thus restricting influx of calcium ions into the cell. The usefulness of nimodipine in patients with Alzheimer's disease and vascular dementia and unspecified dementia is still controversial with mixed results. In spite of the uncertainties about its efficacy in dementia, nimodipine is currently a frequently prescribed drug for cognitive impairment and dementia in several European countries. This review will be conducted in two phases; the current review is based on evidence from published data only. The second phase will be based on individual-patient data analysed centrally and added to this review in due course. OBJECTIVES: To determine the clinical efficacy of nimodipine for the symptoms of dementia, either unclassified or according to the major subtypes - Alzheimer's disease, vascular, or mixed Alzheimer's and vascular dementia. SEARCH STRATEGY: The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'nimodipine' and 'isopropyl (2-methoxy-ethyl) 1,4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3, 5-pyridinedicarboxylate'. SELECTION CRITERIA: All unconfounded, double-blind, randomised trials in which treatment with nimodipine was administered for more than a day and compared to placebo in patients with dementia, either unclassified or according to the major subtypes - Alzheimer's disease, vascular, or mixed Alzheimer's and vascular dementia. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers and the odds ratio (95%CI) or the average difference (95%CI) were estimated. Both intention-to-treat and on-treatment results were extracted. MAIN RESULTS: This review produced no clear results. Many of the data published were not capable of being sensibly pooled. The data were compatible with nimodipine producing improvement, no change or even harm for those with Alzheimer's disease, vascular dementia, or mixed Alzheimer's and vascular dementia. It was not possible to use many of the published results in a combined analysis. For measures of overall clinical improvement, the intention-to-treat analysis, based on one study only, failed to detect any difference between nimodipine and placebo (OR 0.53; 95%CI 0.25 - 1.13). An on-treatment analysis, based on one study only, produced a statistically significant difference in favour of nimodipine (SMD 4.4; 95%CI 3.9 - 5.0). For cognitive function, the effect of nimodipine was statistically significantly different from placebo for the Mini Mental State Examination score (0-30; high =good) (SMD 0.9; 95%CI 0.59 - 1.22) and there was a statistically significant effect in favour of treatment for the Wechsler Memory Scale (SMD 0.47; 95%CI 0.17 - 0.77). These analyses were based only on those who completed the study and not intention-to-treat analyses. There were no results presented in a form suitable for pooling for functional autonomy, behaviour, quality of life dependency (eg institutionalization), effect on carer, death, acceptability of treatment (as measured by withdrawal rate, safety (as measured by the incidence of adverse effects, including side effects, leading to withdrawal). REVIEWER'S CONCLUSIONS: This review provides no convincing evidence that nimodipine is a useful treatment for the symptoms of dementia, either unclassified or according to the major subtypes - Alzheimer's disease, vascular, or mixed Alzheimer's and vascular dementia. (ABSTRACT TRUNCATED)

Alzheimer Disease↗
PubMed2005

Gene transfers of vascular endothelial growth factor-A, vascular endothelial growth factor-B, vascular endothelial growth factor-C, and vascular endothelial growth factor-D have no effects on atherosclerosis in hypercholesterolemic low-density lipoprotein-receptor/apolipoprotein B48-deficient mice.

BACKGROUND: The role of vascular endothelial growth factors (VEGFs) in large arteries has been proposed to be either vasculoprotective or proatherogenic. Because VEGF family members are used for human therapy, it is important to know whether they could enhance atherogenesis. We tested the effects of the members of the VEGF gene family on atherogenesis in LDL-receptor/apolipoprotein (apo) B48 double-knockout (LDLR/apoB48) mice using systemic adenoviral gene transfer. METHODS AND RESULTS: Six groups of LDLR/apoB48-deficient mice (n=110) were kept 3 months on a Western-type diet. After 6 weeks of diet, mice were injected via tail vein with recombinant adenoviruses expressing VEGF-A, -B, -C, or -D or LacZ (1 x 10(9) PFU) or rhVEGF-A protein (2 microg/kg) and euthanized 6 weeks later. Also, older mice (n=36) were injected after 4 months on the diet and euthanized 6 weeks later (total time on the diet, 22 weeks) to evaluate the effects of gene transfers on the development of more mature lesions. Aortas were analyzed for the presence of macroscopic lesions, cross-sectional lesion areas, neovascularization, and cellular composition of the lesions. All groups had equivalent plasma cholesterol and triglyceride levels. Gene transfers with recombinant adenoviruses or administration of rhVEGF-A protein had no statistically significant effects on en face atherosclerotic lesions in the aorta, cross-sectional lesion area, neovascularization, or cellular composition of the lesions. CONCLUSIONS: This study shows no proatherogenic effects of adenovirus-mediated gene transfers of VEGF-A, -B, -C, or -D in the LDLR/apoB48-deficient hypercholesterolemic mice, in which lipoprotein profile and atherosclerosis closely resemble those in human disease.

Adenoviridae↗
PubMed2004

Choice of vascular surgery as a specialty: survey of vascular surgery residents, general surgery chief residents, and medical students at hospitals with vascular surgery training programs.

PURPOSE: Under the direction of the Association of Program Directors in Vascular Surgery, a survey was mailed to vascular surgery residents (VSRs), general surgery chief residents (GS-CRs), and fourth-year medical students (MSs) to better define reasons why trainees do and do not choose vascular surgery as a career. METHODS: Questionnaires were mailed to all accredited VSR programs and their associated GS programs in the United States and Canada in 2001 (survey 1) and in 2003 (survey 2) and to 2 medical schools with VSR programs in 2001. A total of 197 VSRs, 169 GS-CRs, and 78 MSs responded (overall program response rate of 78% for VSRs, 46% for GSRs, 20% for MSs). A scoring system was assigned, with 1.0 the least important and 5.0 the most important reasons to choose or not choose vascular surgery. RESULTS: Technical aspects, role of mentors, and complex decision making involved in vascular surgery were the most important reasons that VSRs, GS-CRs, and MSs would choose vascular surgery as a specialty (average scores > or =4.0 for VSRs and GS-CRs; > or =3.5 for MSs). Responses of GS-CRs and VSRs did not vary significantly between surveys 1 and 2, except endovascular capabilities of vascular surgeons had a more important role in choosing vascular surgery, and future loss of patients to other interventionalists had a more important role in not choosing this specialty in the more recent survey of GS-CRs and VSRs. MSs identified lifestyle as a surgical resident (4.3) and as a surgeon (4.2) as the most important negative factors. A training paradigm consisting of 4 years general surgery + 2 years vascular surgery with a GS certificate was favored by 64% of GS-CRs and 48% of VSRs, compared with a paradigm of 5 years + 2 years with a general surgery certificate, which was favored by 29% of GS-CRs and 25% of VSRs, or 3 years + 3 years without a general surgery certificate, favored by 7% of GS-CRs and 27% of VSRs. Of note, 86% of MSs favored 3 years general surgery + 3 years vascular surgery or 2 years general surgery + 4 years vascular surgery compared with longer general surgery training periods. CONCLUSION: These findings may help vascular surgery program directors devise strategies to attract future trainees. The importance of mentorship to general surgery junior residents and medical students in choosing vascular surgery cannot be overestimated. Endovascular capabilities of vascular surgeons have an increasingly positive role in career choice by GS-CRs and VSRs, but these residents express increasing concerns about potential loss of patients to other specialists. Lifestyle concerns are the most important reasons why medical students do not choose vascular surgery as a career.

Adult↗
PubMed1987

Vascular surgery in the United States. Report of the Joint Society for Vascular Surgery--International Society for Cardiovascular Surgery Committee on Vascular Surgical Manpower.

The Joint Committee on Vascular Surgical Manpower was established in 1985 by the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery. It was charged to provide recommendations regarding vascular surgical manpower requirements for the next 15 years. Analysis of National Center for Health Statistics vascular operative rate data and 1690 questionnaire responses from vascular surgeons documented that vascular surgeons performed 235,400 (41%) of the total of 571,000 vascular operations undertaken in 1985. Vascular surgeons performed 87% of 30,000 aortoiliofemoral reconstructions, 77% of 72,000 peripheral vessel bypasses, 75% of 33,000 abdominal aortic aneurysm repairs, 59% of 55,000 angioaccess procedures, and 50% of 107,000 carotid endarterectomies. However, lack of accurate data on caseloads of surgeons who were not vascular specialists precludes precise prediction of manpower requirements for vascular surgery. It is important that surgical leaders and policy makers define the types of vascular surgical procedures that may be undertaken by vascular and other surgeons. Ongoing analyses must include such determinations to establish accurate data for the prediction of future manpower needs for vascular surgery. Furthermore, future manpower studies should be linked to outcome studies to assess not only numbers of surgeons and operations but quality of care as well.

Forecasting↗
PubMed1999

Vascular surgical society of great britain and ireland: review of out-of-hours vascular procedures in a tertiary vascular unit

BACKGROUND: The aim of this study was to review out-of-hours vascular procedures in a tertiary vascular unit. METHODS: The vascular emergencies that presented outside normal working hours (17. 00 to 08.00 hours) in a vascular unit between January and June 1998 were reviewed. Only cases considered to be life or limb threatening and requiring urgent surgical or radiological intervention were assessed. RESULTS: The Table shows that a significant number of vascular emergencies was performed out of hours in one unit. This was, in part, due to an increase in the number of tertiary referrals, which represented 57 per cent of all emergency procedures. Reasons for the tertiary referrals were: no consultant vascular surgeon on call (33 per cent), no consultant interventional radiologist on call (26 per cent), lack of intensive care beds (30 per cent) and complex procedure (11 per cent). The overall mortality rate of patients referred in this period was 15 per cent. The unit has three consultant vascular surgeons, two consultant interventional radio- logists and one vascular specialist registrar. CONCLUSION: The significant increase in out-of-hours vascular emergencies, both surgical and radiological, has placed an enormous demand on senior members of the team. In addition, it has had a significant impact on the unit's elective admissions and waiting lists, in particular those for routine general surgery. To support the growth in complex emergency referrals, senior vascular fellows in both vascular surgery and radiology have been appointed and proposals are underway to restructure local vascular services.

Journal Article↗
PubMed2004

Vascular cognitive disorder: a new diagnostic category updating vascular cognitive impairment and vascular dementia.

Vascular cognitive impairment (VCI) was proposed as an umbrella term to include subjects affected with any degree of cognitive impairment resulting from cerebrovascular disease (CVD), ranging from mild cognitive impairment (MCI) to vascular dementia. VCI may or may not exclude the host of "focal" circumscribed impairments of specialized functions such as language (aphasia), intentional gesture (apraxia), or categorical recognition (agnosia), among others, that may result from a stroke. Therefore, there are no universally accepted diagnostic criteria for VCI. We conclude that this concept could be more useful if it were to be limited to cases of vascular MCI without dementia, by analogy with the concept of amnestic MCI, currently considered the earliest clinically diagnosable stage of Alzheimer disease (AD). In agreement with our view,the Canadian Study on Health and Aging successfully implemented a restricted definition of VCI, excluding cases of dementia (i.e., vascular cognitive impairment no dementia, VCI-ND). The Canadian definition and diagnostic criteria could be utilized for future studies of VCI. This definition excludes isolated impairments of specialized cognitive functions. Vascular dementia (VaD): The main problem of this diagnostic category stems from the currently accepted definition of dementia that requires memory loss as the sine qua non for the diagnosis. This may result in over-sampling of patients with AD worsened by stroke (AD+CVD). This problem was minimized in controlled clinical trials of VaD by excluding patients with a prior diagnosis of AD, those with pre-existing memory loss before the index stroke, and those with amnestic MCI. We propose a definition of dementia in VaD based on presence of abnormal executive control function, severe enough to interfere with social or occupational functioning. Vascular cognitive disorder (VCD): This term, proposed by Sachdev [P. Sachdev, Vascular cognitive disorder. Int J Geriat Psychiatry 14 (1999)402-403.] would become the global diagnostic category for cognitive impairment of vascular origin, ranging from VCI to VaD. It would include specific disease entities such as post-stroke VCI, post-stroke VaD, CADASIL, Binswanger disease, and AD plus CVD. This category explicitly excludes isolated cognitive dysfunctions such as those mentioned above.

Aged↗
PubMed1998

Cutaneous vascular proliferations. Part III. Malignant neoplasms, other cutaneous neoplasms with significant vascular component, and disorders erroneously considered as vascular neoplasms.

In this third and last part of our review of cutaneous vascular proliferations we include malignant vascular neoplasms and a group of heterogeneous cutaneous neoplasms characterized by a significant vascular component. We also review some disorders that, in our opinion, have been erroneously considered as vascular neoplasms. We review the epidemiologic, histogenetic, clinical, and histopathologic aspects of Kaposi's sarcoma in its four distinctive variants (classic, African-endemic, immunosuppressive drug-associated, and AIDS-associated Kaposi's sarcoma). There is still controversy about whether Kaposi's sarcoma represents a reactive vascular proliferation or a true neoplastic proliferation. In any event, most authors believe that Kaposi's sarcoma does not produce metastatic disease, but rather develops in multifocal fashion. However, Kaposi's sarcoma may cause death, especially in immunosuppressed patients. Epithelioid hemangioendothelioma, Dabska's tumor, and retiform hemangioendothelioma are examples of low-grade angiosarcoma. In contrast, cutaneous angiosarcomas, including the clinical variants of angiosarcoma of face and scalp in elderly patients, angiosarcoma associated with lymphedema, and radiation-induced angiosarcoma are highly aggressive neoplasms with poor prognosis and most patients die within a short period after presentation. A group of benign and relatively frequent cutaneous neoplasms, including multinucleate cell angiohistiocytoma, angiofibroma, angioleiomyoma, angiolipoma, cutaneous angiolipoleiomyoma, and cutaneous angiomyxoma are here covered because of their significant vascular component. Finally, we review briefly a series of cutaneous disorders that have been erroneously considered as vascular neoplasms. Kimura's disease is an inflammatory reactive condition of unknown origin, "benign" angioendotheliomatosis is a reactive intravascular proliferation of endothelial cells that occurs in the skin as a response to a variety of stimuli, "malignant" angioendotheliomatosis is an intravascular lymphoma, and acral pseudolymphomatous angiokeratoma of children (APACHE) is better interpreted as a pseudolymphoma.

Angiofibroma↗
PubMed1999

Can vascularization improve the surgical outcome of the intercostal nerve transfer for traumatic brachial plexus palsy? A clinical comparison of vascularized and non-vascularized methods.

It is very difficult to design a well-controlled comparative study for clarifying the value of vascularized nerve grafting in clinical cases. In order to understand whether or not the vascularizing procedure has any clinical value in nerve transfer and in nerve grafting, we compared non-vascularized with vascularized intercostal nerve transfer in patients with brachial plexus injury. Factors that were likely to affect the results were controlled. We found there was no significant difference in the functional outcome and no difference in the regenerating rate of the nerves between nonvascularized and vascularized intercostal nerve transfer. We concluded that the vascularizing procedure had little clinical value not only in intercostal nerve transfer, but also in nerve grafting irrespective of the length of the gap, when the recipient bed had normal vascularity.

Adolescent↗
PubMed2003

Effects of the prostaglandin I2 analogue, beraprost sodium, on vascular cell adhesion molecule-1 expression in human vascular endothelial cells and circulating vascular cell adhesion molecule-1 level in patients with type 2 diabetes mellitus.

Beraprost sodium is an orally active prostaglandin (PG)I(2) analogue, which has antiplatelet and vasodilating properties. In this study, we investigated the effects of beraprost on the expression of vascular cell adhesion molecule-1 (VCAM-1), one of the key molecules involved in atherosclerosis, in cultured vascular endothelial cells. In addition, we examined the effects of beraprost on circulating VCAM-1 level and atherosclerosis progression in patients with type 2 diabetes mellitus. Beraprost significantly decreased tumor necrosis factor-alpha (TNF-alpha)-induced VCAM-1 expression in human vascular endothelial cells. Beraprost also repressed human monocytoid U937 cell adhesion to the vascular endothelial cells. Twenty-five patients with type 2 diabetes mellitus who had atherosclerotic change of carotid arteries were enrolled for an open prospective study: 11 patients received beraprost for 3 years, while the other 14 did not. The 3-year changes of circulating VCAM-1 level, as well as those of carotid arterial intima-media thickness (IMT) were significantly lower in the patients receiving the beraprost treatment than that in the patients without the treatment. Thus, beraprost had an ability to repress the expression of VCAM-1 in human vascular endothelial cells. In addition, beraprost lowered circulating VCAM-1 level and prevented the increase of carotid IMT in patients with type 2 diabetes mellitus. Considering that circulating VCAM-1 and IMT are predictive of future vascular events, beraprost may have a beneficial effect on progression of atherosclerosis in diabetic patients.

Carotid Arteries↗
PubMed1999

Lack of lymphatic vascular specificity of vascular endothelial growth factor receptor 3 in 185 vascular tumors.

BACKGROUND: Among the molecules important to angiogenesis and lymphangiogenesis is vascular endothelial growth factor receptor 3 (VEGFR-3), a member of the receptor tyrosine kinases of endothelial cells. This receptor is expressed consistently in normal lymphatics, lymphangiomas, and in Kaposi sarcoma, but data regarding other vascular tumors are scant. METHODS: In this study the authors immunohistochemically examined VEGFR-3 expression in 82 benign, 31 borderline, and 72 malignant vascular tumors using a monoclonal antibody to VEGFR-3, heat-induced epitope retrieval, and an avidin-biotin-peroxidase detection system. RESULTS: Although normal mesenchymal tissues showed VEGFR-3 only in the lymphatics, benign and malignant vascular tumors and neovascularization of nonendothelial tumors showed widespread VEGFR-3 distribution. All lymphangiomas and Kaposi sarcomas showed consistent VEGFR-3 reactivity. Among the hemangiomas, spindle cell hemangiomas and 80% of capillary (including all lobular capillary hemangiomas) were positive whereas the endothelium of cavernous, venous, and epitheloid hemangiomas were positive in a minority of cases (20%, 27%, and 33%, respectively). Among the borderline lesions, Kaposiform hemangioendotheliomas were intensely positive whereas epithelioid hemangioendotheliomas were positive in 11 of 29 cases (38%). Angiosarcomas showed VEGRF-3 reactivity in the majority of cases (48 of 60 cases; 80%). The nonepithelioid variants more often were positive (40 of 45 cases; 89%) than the epithelioid variants, of which 8 of 15 (53%) showed positive tumor cells. Nonvascular tumors (including perivascular tumors, other sarcomas, melanomas, carcinomas, and large cell lymphomas) consistently were negative whereas tumor neovascularization commonly was VEGFR-3 positive. CONCLUSIONS: The results of the current study show that although VEGFR-3 shows specificity toward lymphatics in normal tissues, this receptor is distributed extensively in benign and malignant vascular tumors and therefore can be considered a novel marker in the assessment of endothelial cell differentiation of vascular neoplasms.

Biomarkers, Tumor↗
PubMed2005

Role of vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 in the vasodilator response to vascular endothelial growth factor in the neonatal piglet lung.

OBJECTIVE: Vascular endothelial growth factor (VEGF) regulates vascular proliferation and causes vasodilation. In the pulmonary circulation, the vasorelaxing effect of VEGF has been attributed to nitric oxide, whereas in other vascular beds, prostacyclin and other mechanisms are also involved. This vascular effect follows binding to two receptors, VEGF receptor 1 (VEGFR1) and VEGF receptor 2 (VEGFR2), the latter of which is thought to be the main receptor responsible for the vasorelaxing effect of VEGF. The role of VEGFR1 in the neonatal pulmonary vasculature remains to be determined. DESIGN: Prospective randomized laboratory investigation. SETTING: Animal laboratory. SUBJECTS: Newborn Yorkshire-Landrace piglets. INTERVENTIONS: To determine the mechanisms of action of VEGF in the neonatal pulmonary vasculature, the effect of VEGF (10-10 M) was tested in isolated perfused piglet lungs, alone and in the presence of a VEGFR2 kinase inhibitor, N-nitro-l-arginine (L-NNA), indomethacin (Indo), L-NNA + Indo, and GF109203X, a protein kinase C inhibitor. The effect of a VEGFR1 agonist, placenta growth factor (PlGF), was also studied with or without L-NNA. Perfusate was collected, and cyclic guanosine monophosphate (cGMP), as well as 6-keto prostaglandin F1alpha and thromboxane B2, the stable metabolites of prostacyclin and thromboxane, respectively, was measured. MEASUREMENTS AND MAIN RESULTS: VEGF caused vasorelaxation with a concomitant increase in cGMP. PlGF also decreased vascular tone and increased cGMP. VEGFR2 kinase inhibitor did not prevent the reduction in perfusion pressure seen with VEGF but blocked the increase in cGMP. Pretreatment with L-NNA completely inhibited VEGF and PlGF vasodilation and prevented the increase in cGMP seen with both agonists. Pretreatment with Indo or GF109203X did not reduce the dilator response to VEGF. CONCLUSIONS: VEGF vasodilation may follow nitric oxide release in the piglet pulmonary circulation. VEGF vasorelaxation may not only occur through binding to VEGFR2, since PlGF, the specific VEGFR1 agonist, also causes vasodilation. Therefore, vasodilator response to VEGF may involve both types of receptor in the neonatal piglet pulmonary vasculature.

Animals↗
PubMed1996

Regulation of endothelial production of C-type natriuretic peptide in coculture with vascular smooth muscle cells. Role of the vascular natriuretic peptide system in vascular growth inhibition.

Recently, we have demonstrated that C-type natriuretic peptide (CNP) is produced in vascular endothelial cells (ECs). In the present study, we investigated the interaction of ECs and vascular smooth muscle cells (SMCs) for endothelial production of CNP and its action on vascular growth, using the EC/SMC coculture system. The concentration of CNP-like immunoreactivity in the medium was increased 60-fold within 48 hours in the EC/SMC coculture with direct contact compared with that in EC alone. Northern blot analysis revealed the augmented expression of CNP mRNA in the EC/SMC coculture. The accumulation of intracellular cGMP in the coculture was concomitantly increased, and this response was blocked by anti-CNP monoclonal antibody and HS-142-1, a nonpeptide atrial natriuretic peptide receptor antagonist. The concentration of biologically active transforming growth factor-beta (TGF-beta) in the culture medium of the coculture with direct contact of ECs and SMCs was elevated to the level to stimulate endothelial production of CNP. Actually, the neutralizing antibody against TGF-beta abrogated the cGMP accumulation in the coculture. These results show that endothelial production of CNP in the EC/SMC coculture is at least in part regulated by TGF-beta. Furthermore, the conditioned medium from ECs stimulated by TGF-beta was demonstrated to have a growth-inhibitory effect on SMCs, which was abolished by anti-CNP monoclonal antibody and HS-142-1. The treatment with anti-CNP monoclonal antibody and HS-142-1 also significantly increased the cell number of the EC/SMC coculture. The present study reveals the pathophysiological significance of endothelial CNP as a paracrine/autocrine vascular regulator for vascular growth in the interaction of ECs and SMCs.

Animals↗