Vascular Endothelial Growth Factor Promotes Proliferation and Migration of Cavernous Smooth Muscle Cells

Liu, Xiaowei; Lin, C. C.; Graziottin, Túlio M.; Resplande, Júlio; Lue, Tom F.

doi:10.1016/s0022-5347(05)66158-7

Cited by 53 publications

(18 citation statements)

References 21 publications

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“…Penile erection is a vascular event that is primarily regulated by the relaxation of the arterial and corporal smooth muscles, which play a major role in modulating penile blood flow during erection and detumescence 12 . Recent reports indicated a role for angiogenic growth factors such as VEGF in the modulation of rat penile vascularity 4 . This was supported by in vivo demonstration that the intracavernosal injection of VEGF, as well as adenovirus‐mediated VEGF gene therapy, 13 lessened ED in aged rats 14 .…”

Section: Discussionmentioning

confidence: 90%

“…Angiogenesis, a process by which new blood vessels are formed from preexisting ones, is thought to be regulated by the balance between angiogenesis inducers and inhibitors 3 . VEGF (vascular endothelial growth factor) is an endothelial cell‐specific mitogen, a smooth muscle cell promoter of migration and proliferation, 4 and is the major vascular growth factor involved in physiologic and pathologic angiogenesis 5 . VEGF is essential for endothelial cell survival, and binds specifically to both tyrosine kinase membrane receptors, Flt‐1 (fms‐like tyrosine kinase‐1 receptor) and KDR/Flk‐1 (kinase insert domain‐containing receptor).…”

Section: Introductionmentioning

confidence: 99%

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Aging and Orchidectomy Modulate Expression of VEGF Receptors (Flt‐1 and Flk‐1) on Corpus Cavernosum of the Rat

Neves

Santos

Tomada

et al. 2006

Annals of the New York Academy of Sciences

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Aging and hypogonadic states are known risk factors for erectile dysfunction (ED), contributing together to vascular damage of penile tissue. In the present study, VEGF-specific membrane receptor (VEGFR-1/Flt-1 and VEGFR-2/Flk-1) expression was studied by confocal immunofluorescence in the corpus cavernosum of control rats, rats aged 12 and 18 months, and orchidectomized Wistar rats (90 days of bilateral orchidectomy). Immunocytochemical results demonstrated VEGFR-2 expression restricted to the endothelium in both control and orchidectomized rats. Aged animals (12 and 18 months) presented enlarged vessels with intense VEGFR-2 endothelial staining. On the other hand, VEGFR-1 was demonstrated in smooth muscle fibers, particularly in those that surround vessel endothelium, the endothelial expression being very low in control and orchidectomized rats. However, in the aged rats, a shift resulting in a VEGFR-1 and VEGFR-2 co-localization in the endothelial cell was observed. The findings suggest an upregulation of VEGFR-1 in the corpora cavernosa during aging in the rat, which is evident from an increased expression by endothelial cells.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Aging and Orchidectomy Modulate Expression of VEGF Receptors (Flt‐1 and Flk‐1) on Corpus Cavernosum of the Rat

Neves

Santos

Tomada

et al. 2006

Annals of the New York Academy of Sciences

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“…We use GFP to label MDSCs in this study. GFP is non‐toxic to cells and can be observed in whole cells and is one of the best labeling techniques for quantitative analysis of the transplanted cells in vivo [31,32]. Using this tracking method, we find that the number of GFP‐positive MDSCs in the corpus cavernosum of MDSCs/VEGF groups is significantly higher than that in the MDSCs/vector group at different time points after cells transplantation (Figure 5).…”

Section: Discussionmentioning

confidence: 93%

The Therapeutic Role of VEGF-Expressing Muscle-Derived Stem Cells in Acute Penile Cavernosal Injury

Wei

et al. 2012

The Journal of Sexual Medicine

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Introduction Traumatic penile injury is one of the urological emergencies. Surgery and conservative management are major treatment methods but are always accompanied by many complications. Aim To investigate the feasibility of repairing cavernous tissues in acute rabbit penile cavernosal injury model with vascular endothelial growth factor (VEGF)-expressing muscle-derived stem cells (MDSCs). Methods MDSCs were isolated and transfected with hVEGF165 lentiviral gene vector in vitro. The expression of VEGF was confirmed using enzyme-linked immunosorbent assay (ELISA), Western blot, and real-time polymerase chain reaction (PCR) analyses. After animal models were constructed, animals were randomly divided into four groups, which were administrated with MDSCs/VEGF, MDSCs/vector, MDSCs, and normal saline, respectively. A month later, magnetic resonance imaging (MRI) and intracavernosal pressures (ICP) were performed on the animals. Then penile tissues were harvested and assayed with Western blot and immunohistochemistry. Main Outcome Measures Real-time PCR, Western blot, ELISA, immunohistochemistry, MRI, and ICP were performed in our experiments. Results The expression of VEGF significantly increased in the VEGF-expressing MDSCs group compared with those in the MDSCs/vector and MDSCs groups. VEGF protein expression in the injury sites of cavernous tissues were significantly higher in the MDSCs/VEGF group compared with those in other three groups. Immunohistochemical staining showed that α-smooth muscle actin-positive cells, von Willebrand factor-positive cells and capillary density markedly increased in the MDSCs/VEGF group. Animals receiving MDSCs/VEGF showed a significant improvement in cavernosal contractile function and structural repair. Conclusions The transplantation of VEGF-expressing MDSCs could repair the actuely injured cavernous tissue. We believed that it could be a novel therapeutic strategy for acute rabbit penile cavernosal injury.

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“…Increased oxygen tension, testosterone and insulinlike growth factor and endothelial growth factor have been associated with increasing smooth muscle content [30], whereas chronic ischaemia, ageing, and neurogenic compromise have been implicated in the promotion of intracorporeal fibrosis [31]. Increased oxygen tension, testosterone and insulinlike growth factor and endothelial growth factor have been associated with increasing smooth muscle content [30], whereas chronic ischaemia, ageing, and neurogenic compromise have been implicated in the promotion of intracorporeal fibrosis [31].…”

Section: Discussionmentioning

confidence: 99%

A histological and immunohistochemical study on human penile cavernosal tissue with viewpoints of venogenic erectile dysfunction

Radwan¹,

Kamel

2011

The Egyptian Journal of Histology

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ObjectiveTo determine the histological and immunohistochemical alterations of human penile cavernosal tissue in venogenic erectile dysfunction (ED) compared with potent controls regarding collagen fibres, elastic fibres, smooth muscle content and inducible nitric oxide synthase (i-NOS) expression. Materials and methodsCavernous biopsies were obtained from four potent men (two with penile fracture and two with congenital penile curvature) regarded as controls and from 15 patients with venogenic ED undergoing implantation of penile prosthesis. The specimens obtained were subjected to haematoxylin and eosin, Masson's trichrome and orcein stains and antismooth muscle a-actin and i-NOS immunostaining. Evaluation was carried out using computerized morphometric analysis and results were statistically compared. Results A significant increase of collagen fibres with reduced smooth muscle and elastic fibre content was shown in patients with venogenic ED compared with controls. There was also an increased expression of i-NOS immuonoreactivity. ConclusionHistological alterations of cavernosal tissue structure in venogenic ED point to progressive fibrosis. Early diagnosis by penile biopsy may help to combat fibrosis and preserve the integrity of erectile tissue and accordingly the penile erection.

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Vascular Endothelial Growth Factor Promotes Proliferation and Migration of Cavernous Smooth Muscle Cells

Cited by 53 publications

References 21 publications

Aging and Orchidectomy Modulate Expression of VEGF Receptors (Flt‐1 and Flk‐1) on Corpus Cavernosum of the Rat

Aging and Orchidectomy Modulate Expression of VEGF Receptors (Flt‐1 and Flk‐1) on Corpus Cavernosum of the Rat

The Therapeutic Role of VEGF-Expressing Muscle-Derived Stem Cells in Acute Penile Cavernosal Injury

A histological and immunohistochemical study on human penile cavernosal tissue with viewpoints of venogenic erectile dysfunction

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