Vascular Endothelial Growth Factor: Basic Science and Clinical Progress

Ferrara, Napoleone

doi:10.1210/er.2003-0027

Cited by 3,254 publications

(2,749 citation statements)

References 363 publications

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“…[7][8][9][10] However, prolonged cardiac hypertrophy leads to cardiac ischemia as a result of the reduction in myocardial capillary density. This reduction is one of Low Na Veh Hyd Irb Tem Figure 5 Effect of hydralazine, tempol and irbesartan on cardiacVEGF (a) and phospho-ASK1 (b) of DS rats.…”

Section: Discussionmentioning

confidence: 99%

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Novel mechanism of angiotensin II-induced cardiac injury in hypertensive rats: the critical role of ASK1 and VEGF

et al. 2011

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This study was undertaken to elucidate a novel mechanism underlying angiotensin II-induced cardiac injury, focusing on the role of oxidative stress and myocardial capillary density. Salt-loaded Dahl salt-sensitive hypertensive rats (DS rats), a useful model for hypertensive cardiac remodeling or heart failure, were orally given irbesartan (an AT1 receptor blocker), tempol (a superoxide dismutase mimetic) or hydralazine (a vasodilator). Irbesartan significantly ameliorated left ventricular ischemia and prevented the development of cardiac hypertrophy and fibrosis in DS rats. The benefits were associated with the attenuation of oxidative stress, normalization of myocardial capillary density and inhibition of capillary endothelial apoptosis. Moreover, DS rats with significant cardiac hypertrophy and fibrosis displayed decreased myocardial vascular endothelial growth factor (VEGF) expression and increased cardiac apoptosis signal-regulating kinase 1 (ASK1) activation. Treatment with irbesartan significantly reversed these phenotypes. Tempol treatment of DS rats mimicked all the above-mentioned effects of irbesartan, indicating the critical role of oxidative stress in cardiac injury. We also investigated the role of VEGF and ASK1 in oxidative stress-induced endothelial apoptosis by using cultured endothelial cells from wild-type and ASK1-deficient mice. Oxidative stress-induced ASK1 activation led to endothelial apoptosis, and VEGF treatment prevented oxidative stress-induced endothelial apoptosis by inhibiting ASK1 activation. We obtained the first evidence that oxidative stress-induced cardiac VEGF repression and ASK1 activation caused the enhancement of endothelial apoptosis and contributed to a decrease in myocardial capillary density. These effects resulted in angiotensin II-induced progression of cardiac injury.

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Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10] Therefore, recent work has focused on examining the regulatory mechanisms of capillary density in cardiac hypertrophy. However, the role of angiotensin II in the regulation of capillary density during cardiac hypertrophy is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Novel mechanism of angiotensin II-induced cardiac injury in hypertensive rats: the critical role of ASK1 and VEGF

et al. 2011

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“…1 Formation of new blood vessels caused by the overproduction of growth factors such as VEGF is a key component of diseases such as wet age-related macular degeneration (AMD), proliferative diabetic retinopathy (PDR) and tumor growth. [2][3][4] Blocking of VEGF with antibodies, soluble VEGF receptors (sVEGFR) or inhibition of VEGF receptor (VEGFR) tyrosine kinase activity are useful strategies that have shown promising preclinical and clinical results. [4][5][6] Ranibizumab, an anti-VEGF drug given intravitreally to wet-AMD patients results in substantially improved visual acuity.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4] Blocking of VEGF with antibodies, soluble VEGF receptors (sVEGFR) or inhibition of VEGF receptor (VEGFR) tyrosine kinase activity are useful strategies that have shown promising preclinical and clinical results. [4][5][6] Ranibizumab, an anti-VEGF drug given intravitreally to wet-AMD patients results in substantially improved visual acuity. 7 Intraocular gene delivery of VEGF antagonists could have theoretical advantages over the current treatment, which requires monthly intravitreal injections (for years) by a retinal specialist.…”

Section: Introductionmentioning

confidence: 99%

Novel anti-VEGF chimeric molecules delivered by AAV vectors for inhibition of retinal neovascularization

Pecháň¹,

Rubin²,

Lukason³

et al. 2008

Gene Ther

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“…Increased vascular endothelial growth factor (VEGF) expression is associated with many angiogenesis dependent pathologies, such as cancer (Ferrara, 2004) and ocular diseases (Gariano et al, 2006). Therefore, intensive efforts have been undertaken over the past decade to develop therapeutic strategies in order to inhibit the pathological angiogenesis via neutralization of VEGF or its receptors by antibodies, or blocking VEGF receptor activation and signaling with tyrosine kinase inhibitors (Ellis and Hicklin, 2008).…”

Section: Introductionmentioning

confidence: 99%

A novel concept in antiangiogenic and antitumoral therapy: multitarget destabilization of short-lived mRNAs by the zinc finger protein ZFP36L1

et al. 2010

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Angiogenesis inhibitors have shown clinical benefits in patients with advanced cancer, but further therapeutic improvement is needed. We have previously shown that the zinc finger protein 36, C3H type-like 1 (ZFP36L1) enhances vascular endothelial growth factor (VEGF) mRNA decay through its interaction with AU-rich elements within VEGF 3 0 -untranslated region. In this study, we evaluated the possibility to develop an antiangiogenic and antitumoral strategy using the mRNA-destabilizing activity of ZFP36L1. We engineered a cell-penetrating ZFP36L1, by fusing it to the protein transduction domains (PTDs) TAT derived from HIV, or the polyarginine peptides R7 or R9. PTD-ZFP36L1 fusion proteins were expressed in bacterial cells and affinity-purified to homogeneity. TAT-, R7-and R9-ZFP36L1 were efficiently internalized into living cells and decreased both endogenous VEGF mRNA half-life and VEGF protein levels in vitro. Importantly, a single injection of R9-TIS11b fusion protein into a high-VEGF expressing tissue in vivo (in this study, the mouse adrenal gland) markedly decreased VEGF expression. We further evaluated the effect of R9-ZFP36L1 on tumor growth using Lewis Lung Carcinoma (LL/2) cells implanted subcutaneously into nude mice. Intratumoral injection of R9-ZFP36L1 significantly reduced tumor growth and markedly decreased the expression of multiple angiogenic and inflammatory cytokines, including VEGF, acidic fibroblast growth factor, tumor necrosis factor a, interleukin (IL)-1a and IL-6, with a concomitant obliteration of tumor vascularization. These findings indicate that R9-ZFP36L1 fusion protein may represent a novel antiangiogenic and antitumoral agent, and supports the emerging idea that modulation of mRNA stability represents a promising therapeutic approach to treat cancer.

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Vascular Endothelial Growth Factor: Basic Science and Clinical Progress

Cited by 3,254 publications

References 363 publications

Novel mechanism of angiotensin II-induced cardiac injury in hypertensive rats: the critical role of ASK1 and VEGF

Novel mechanism of angiotensin II-induced cardiac injury in hypertensive rats: the critical role of ASK1 and VEGF

Novel anti-VEGF chimeric molecules delivered by AAV vectors for inhibition of retinal neovascularization

A novel concept in antiangiogenic and antitumoral therapy: multitarget destabilization of short-lived mRNAs by the zinc finger protein ZFP36L1

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