Abstract:
:Thrombospondin-1 (TSP1) is a potent natural inhibitor of angiogenesis. Although TSP1 has been reported to induce endothelial cell apoptosis in vitro and to downregulate neovascularization in vivo, the molecular mechanisms that link these two processes have yet to be established. Here we report that TSP1 mediates endothelial cell apoptosis and inhibits angiogenesis in association with increased expression of Bax, decreased expression of Bcl-2, and processing of caspase-3 into smaller proapoptotic forms. The ability of TSP1 to induce both endothelial cell apoptosis in vitro and to suppress angiogenesis in vivo was blocked by the caspase-3 inhibitor z-DEVD-FMK. TSP1 also attenuated VEGF-mediated Bcl-2 expression in endothelial cells in vitro and angiogenesis in vivo. Furthermore, TSP1 induced endothelial cell apoptosis and inhibited neovascularization in sponge implants in SCID mice. We conclude that TSP1 induces endothelial cell apoptosis and inhibits neovascularization by altering the profile of survival gene expression and activating caspase-3.
journal_name
J Vasc Resjournal_title
Journal of vascular researchauthors
Nör JE,Mitra RS,Sutorik MM,Mooney DJ,Castle VP,Polverini PJdoi
10.1159/000025733keywords:
subject
Has Abstractpub_date
2000-05-01 00:00:00pages
209-18issue
3eissn
1018-1172issn
1423-0135pii
25733journal_volume
37pub_type
杂志文章abstract:BACKGROUND AND AIMS:Vasomotion consists in cyclic oscillations of the arterial diameter induced by the synchronized activity of the smooth muscle cells. So far, contradictory results have emerged in the literature about the role of the endothelium in the onset and maintenance of vasomotion. Here our aim is to understan...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000124283
更新日期:2008-01-01 00:00:00
abstract::The purpose of this study was to determine the contribution of long-chain fatty acids relative to other mitochondrial substrates in active vascular smooth muscle (VSM). Hog carotid arteries were isometrically contracted in physiological saline solution containing 0.71 mM U-(13)C-oleic acid (bound to albumin at a ratio...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000051056
更新日期:2001-05-01 00:00:00
abstract::In response to stimuli, endothelial cells release arachidonic acid, a lipid precursor of various vasoactive substances. We have investigated the relationships between cytosolic Ca2+ movements and arachidonic acid release in human umbilical vein endothelial cells. Histamine, a receptor-dependent agonist, and thapsigarg...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000025647
更新日期:1999-05-01 00:00:00
abstract:PURPOSE:To determine: (1) whether variables of a pulse wave form analysis of ocular microcirculation shown by laser speckle flowgraphy (LSFG) correlate with left ventricular (LV) systolic dysfunction and (2) whether these variables correlate with LV diastolic dysfunction in subjects without LV systolic dysfunction as a...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000494066
更新日期:2018-01-01 00:00:00
abstract::The role of leukocytes (WBCs) and platelets (PLTs) in the pulmonary circulation may be important in the development of monocrotaline (MCT)-induced pulmonary hypertension in rats. We investigated the suppressive effects of long-term prostaglandin E(1) (PGE(1)) aerosol on the changes in WBCs and PLTs in the peripheral b...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000048996
更新日期:2002-01-01 00:00:00
abstract::We tested the hypothesis that oxidized low-density lipoprotein (oxLDL)-induced inactivation of Akt within endothelial progenitor cells (EPCs) is mediated at the level of phosphoinositide 3-kinase (PI3K), specifically by nitrosylation of the p85 subunit of PI3K, and that this action is critical in provoking oxLDL-induc...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000313879
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Hypoxia results in pulmonary hypertension and vascular remodeling due to induction of pulmonary artery cell proliferation. Besides pulmonary artery smooth muscle cells, pulmonary artery endothelial cells (PAECs) are also involved in the development of pulmonary hypertension, but the effect of hypoxia on PAEC...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000327005
更新日期:2011-01-01 00:00:00
abstract:PURPOSE:Hypoxic conditions cause fibroblasts to differentiate into alpha smooth-muscle cell actin (α -SMA)-positive cells, i.e. myofibroblasts. This process is a hallmark of venous neointimal hyperplasia (VNH) associated with hemodialysis vascular access. The purpose of this study was to determine if blood outgrowth en...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000369929
更新日期:2014-01-01 00:00:00
abstract:AIM:Transglutaminase 2 (TG2) is important for the deposition and stability of the extracellular matrix via effects on cross-linking of matrix proteins and transforming growth factor beta (TGFbeta) activity. The purpose of this study was to investigate the effect of TG2 deficiency on the composi- tion of atherosclerotic...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000255966
更新日期:2010-01-01 00:00:00
abstract::Recent research in ultrasound technology has led to the development of a high-resolution echo-tracking device. The present study was performed to evaluate the accuracy in the measurement of human radial artery intima-media thickness with this new device. We determined the correlation between histological and ultrasoni...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000159037
更新日期:1994-03-01 00:00:00
abstract:AIMS:The effects of ischemia and hypercholesterolemia on the function and morphological adaptation of the rabbit hindlimb were assessed. METHODS:In rabbits on normal or cholesterol diet, experiments were performed on days 0-28 following bilateral femoral artery ligation. Calf blood pressure (C(BP)), exercise tolerance...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000113600
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Angiopoietin-like protein 3 (ANGPTL3) is a liver-derived plasma protein that modulates plasma triglyceride clearance, angiogenesis and atherosclerosis in experimental models. So far, no study has examined its role in atherosclerosis in human subjects. We evaluated the possible association between plasma ANGP...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000098153
更新日期:2007-01-01 00:00:00
abstract::The pH has marked effects on the blood flow in several vascular beds but the underlying mechanisms remain incompletely understood. It is still not agreed, for example, whether it is the fall in extracellular pH or intracellular pH that is responsible for changes in tone resulting from hypercapnic acidosis. The issue h...
journal_title:Journal of vascular research
pub_type: 杂志文章,评审
doi:10.1159/000159163
更新日期:1996-09-01 00:00:00
abstract:OBJECTIVES:Hyperuricemia provokes endothelial dysfunction (ECD). Decreased endothelial nitric oxide synthase (eNOS) activity is an important source of ECD. Cationic amino acid transporter-1 (CAT-1) is the specific arginine transporter for eNOS. We hypothesize that hyperuricemia inhibits arginine uptake. METHODS:Experi...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000320356
更新日期:2011-01-01 00:00:00
abstract::The aim of this study was to use periarterial manipulation to produce an atheroma-like neo-intima in rabbits and study resting blood flow and vascular responsiveness in vivo. One common carotid artery was enclosed in a silastic collar to induce a neo-intima similar to that of human early atherosclerosis, and carotid b...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000159043
更新日期:1994-07-01 00:00:00
abstract::The effect of shear stress at the endothelium in the attenuation of the noradrenaline-induced constriction of the femoral vascular bed perfused at a constant blood flow was investigated in 16 anesthetized cats. It is known that the adrenergic vasoconstriction of the femoral vascular bed is considerably greater at a co...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000097750
更新日期:2007-01-01 00:00:00
abstract::Dynamic visualization of the intravascular events leading to the extravasation of leukocytes into tissues by intravital microscopy has significantly expanded our understanding of the underlying molecular processes. In contrast, the detailed observation of leukocyte transendothelial and interstitial migration in vivo h...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000073902
更新日期:2003-09-01 00:00:00
abstract::Endothelin-1 (ET-1), a vasoconstrictor peptide produced by endothelial and vascular smooth muscle cells (VSMC) might play a role in vascular remodelling. To investigate the proposed 'mitogenic' potential of ET-1, we examined the effects of chronic exposure of VSMC to ET-1 on cell cycle, growth/proliferation and differ...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000158994
更新日期:1993-07-01 00:00:00
abstract::Inflammation is a highly regulated process with common but also specific characteristics in each tissue affected. Recruitment of leukocytes from the blood to the injured tissue is an important early step in the inflammatory cascade. This review highlights the role of connexins (Cxs) in the regulation of both acute and...
journal_title:Journal of vascular research
pub_type: 杂志文章,评审
doi:10.1159/000316942
更新日期:2011-01-01 00:00:00
abstract::The assembly of the vessel wall from its cellular and extracellular matrix components is a critical process in the development and maturation of the cardiovascular system. However, fundamental questions concerning the origin of vessel wall cells and the mechanisms that regulate their development and differentiation re...
journal_title:Journal of vascular research
pub_type: 杂志文章,评审
doi:10.1159/000025622
更新日期:1999-01-01 00:00:00
abstract::Signaling pathways activated by the tachykinin substance P (SP) were investigated in pig coronary artery endothelial cells (PCAECs). Single cells were obtained after enzymatic digestion of coronary arteries. Intracellular Ca2+ ([Ca2+]i) was measured from fura-2 fluorescence while membrane potential or ionic current wa...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000159222
更新日期:1997-05-01 00:00:00
abstract::The present study investigated transcellular signalling mechanism involved in thrombin-induced production of plasminogen activator inhibitor-1 (PAI-1) in cultured vascular baboon aortic smooth muscle cells (BASMC). Treatments with thrombin dose-dependently increased the steady state levels of PAI-1 mRNA and the genera...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000159205
更新日期:1997-03-01 00:00:00
abstract::Cx40-deficient mice (Cx40-/-) are hypertensive due to increased renin secretion. We evaluated the renal expression of neuronal nitric oxide synthase (nNOS) and cyclooxygenases COX-1 and COX-2, three macula densa enzymes. The levels of nNOS were increased in kidneys of Cx40-/- mice, as well as in those of wild-type (WT...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000156704
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:A new method was evaluated where local changes in oxygen tension were induced in a tissue while being studied under a microscope in vivo. We tested whether hypoxic vasodilation and hyperoxic vasoconstriction in arterioles in striated muscle are being propagated upstream, and whether the endothelium and smoot...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000318777
更新日期:2011-01-01 00:00:00
abstract::In this study we aimed to investigate whether the therapeutic efficacy of anisodamine in the treatment of bacteraemic shock could--at least in part--be brought about by its direct interference with the lipopolysaccharide (LPS)-induced activation of endothelial cells. Thus, we investigated the effect of anisodamine on ...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000051025
更新日期:2001-01-01 00:00:00
abstract::The pathophysiology of Raynaud's phenomenon (RP) remains an enigma. Whatever theories proposed, the final event leading to the clinical symptoms is the occlusion of digital vessels. However, the possibility that the upstream large arterial vessels contribute to vasopasm has never been investigated. We used a high reso...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000159237
更新日期:1997-07-01 00:00:00
abstract::Although the content of histamine in myocardial tissue is high, its contribution to the regulation of coronary blood flow has not been clearly defined. The aim of the present study was to investigate whether or not nitric oxide (NO), an important modulator of coronary vascular tone, is involved in histamine-induced co...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000158987
更新日期:1993-05-01 00:00:00
abstract:PURPOSE:Exercise elicits early adaptation of coronary vessels enabling the coronary circulation to respond adequately to higher flow demands. We hypothesized that short-term daily exercise induces biomechanical and functional remodeling of the coronary resistance arteries related to pressure. METHODS:Male rats were su...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000486571
更新日期:2018-01-01 00:00:00
abstract::This study utilised catecholamine fluorescence histochemistry, multiple-labelling immunohistochemistry and retrograde axonal transport to determine the distribution and neuropeptide content of sympathetic neurons innervating veins in the dorsal skin of the guinea pig pinna. There was a dense plexus of sympathetic axon...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000159113
更新日期:1995-11-01 00:00:00
abstract:BACKGROUND:It has been reported that smoking is one of the strongest positive risk factors for abdominal aortic aneurysms (AAAs). Although many studies have been directed to decipher the effect of smoking on AAA, its effect on macrophage activation has not yet been explored. OBJECTIVES:We have reported the importance ...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000498893
更新日期:2019-01-01 00:00:00