The Effect of Vascular Endothelial Growth Factor on a Rat Model of Traumatic Arteriogenic Erectile Dysfunction

LEE, MING-CHAN; El‐Sakka, Ahmed I.; Graziottin, Túlio M.; Ho, Hao-Chung; Lin, C. C.; Lue, Tom F.

doi:10.1097/00005392-200202000-00080

Cited by 43 publications

(52 citation statements)

References 31 publications

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“…Therefore, neovascularization has emerged as a strategy for treating vasculogenic ED and is anticipated to be more effective for patients with moderate to severe ED and to restore physiologic erections, i.e., spontaneity of the sexual act. Local intracavernous delivery of the vascular endothelial growth factor-A (VEGF-A) gene or protein has been shown to restore erectile function in animal models of vasculogenic ED7151617. However, treatment with exogenous VEGF-A often results in a pathologic angiogenesis producing leaky, inflamed, and disorganized blood vessels in experimental systems1819, greatly compromising its therapeutic value.…”

mentioning

confidence: 99%

Designed angiopoietin-1 variant, COMP-angiopoietin-1, rescues erectile function through healthy cavernous angiogenesis in a hypercholesterolemic mouse

Ryu

Kim

Koh

et al. 2015

Sci Rep

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Despite the advent of oral phosphodiesterase-5 inhibitors, curative treatment for erectile dysfunction (ED) remains unavailable. Recently, the link between ED and cardiovascular disease was unveiled and the main etiology of ED was found to be vasculogenic. Therefore, neovascularization is a promising strategy for curing ED. Angiopoietin-1 (Ang1) is an angiogenic growth factor that promotes the generation of stable and functional vasculature. Here, we demonstrate that local delivery of the soluble, stable, and potent Ang1 variant, COMP-Ang1 gene or protein, into the penises of hypercholesterolemic mice increases cavernous angiogenesis, eNOS phosphorylation, and cGMP expression, resulting in full recovery of erectile function and cavernous blood flow up to 8 weeks after treatment. COMP-Ang1-induced promotion of cavernous angiogenesis and erectile function was abolished in Nos3-/- mice and in the presence of the NOS inhibitor, L-NAME. COMP-Ang1 also restored the integrity of endothelial cell-cell junction by down-regulating the expression of histone deacetylase 2 in the penis of hypercholesterolemic mice and in primary cultured mouse cavernous endothelial cells. These findings constitute a new paradigm toward curative treatment of both cavernous angiopathy and ED.

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mentioning

confidence: 99%

Designed angiopoietin-1 variant, COMP-angiopoietin-1, rescues erectile function through healthy cavernous angiogenesis in a hypercholesterolemic mouse

Ryu

Kim

Koh

et al. 2015

Sci Rep

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“…Although no direct evidence, such as collateral circulation building or regrowth of new blood vessels, has demonstrated autocompensation occurred in the BIIAL, HFD and BCH groups at 12 weeks, the erectile function of these three groups decreased immediately after injuring according to previous report [12]. Indeed, our results indicate erectile function, such as ICP/MAP, nNOS and eNOS, in BIIAL and HFD groups are much better than that in BCH group, which hints that more erectile function is restored in BIIAL and HFD groups rather than that in BCH group, though the extent is modest, as well as Lee's work [12]. Future work concentrating on autocompensation at different time points would be expected to clarify the specific mechanism.…”

Section: Discussionmentioning

confidence: 71%

“…For example, Bakircioglu reported that 4 months were necessary to establish a hyperlipidemia-induced ED model in rats, and Metze had reported severe sexual dysfunction after major pelvic trauma [11], [21]. Lee successfully developed a traumatic arteriogenic ED rat model, but ED may occur only in the acute phase and erectile function may show autocompensation at 6 weeks after surgery [12], [16]. Although no direct evidence, such as collateral circulation building or regrowth of new blood vessels, has demonstrated autocompensation occurred in the BIIAL, HFD and BCH groups at 12 weeks, the erectile function of these three groups decreased immediately after injuring according to previous report [12].…”

Section: Discussionmentioning

confidence: 99%

“…Lee successfully developed a traumatic arteriogenic ED rat model, but ED may occur only in the acute phase and erectile function may show autocompensation at 6 weeks after surgery [12], [16]. Although no direct evidence, such as collateral circulation building or regrowth of new blood vessels, has demonstrated autocompensation occurred in the BIIAL, HFD and BCH groups at 12 weeks, the erectile function of these three groups decreased immediately after injuring according to previous report [12]. Indeed, our results indicate erectile function, such as ICP/MAP, nNOS and eNOS, in BIIAL and HFD groups are much better than that in BCH group, which hints that more erectile function is restored in BIIAL and HFD groups rather than that in BCH group, though the extent is modest, as well as Lee's work [12].…”

Section: Discussionmentioning

confidence: 99%

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A Novel Method to Establish a Rat ED Model Using Internal Iliac Artery Ligation Combined with Hyperlipidemia

Wang

Dong

et al. 2014

PLoS ONE

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ObjectiveTo investigate a novel method, namely using bilateral internal iliac artery ligation combined with a high-fat diet (BCH), for establishing a rat model of erectile dysfunction (ED) that, compared to classical approaches, more closely mimics the chronic pathophysiology of human ED after acute ischemic insult.Materials and MethodsForty 4-month-old male Sprague Dawley rats were randomly placed into five groups (n = 8 per group): normal control (NC), bilateral internal iliac artery ligation (BIIAL), high-fat diet (HFD), BCH, and mock surgery (MS). All rats were induced for 12 weeks. Copulatory behavior, intracavernosal pressure (ICP), ICP/mean arterial pressure, hematoxylin-eosin staining, Masson's trichrome staining, serum lipid levels, and endothelial and neuronal nitric oxide synthase immunohistochemical staining of the cavernous smooth muscle and endothelium were assessed. Data were analyzed by SAS 8.0 for Windows.ResultsSerum total cholesterol and triglyceride levels were significantly higher in the HFD and BCH groups than the NC and MS groups. High density lipoprotein levels were significantly lower in the HFD and BCH groups than the NC and MS groups. The ICP values and mount and intromission numbers were significantly lower in the BIIAL, HFD, and BCH groups than in the NC and MS groups. ICP was significantly lower in the BCH group than in the BIIAL and HFD groups. Cavernous smooth muscle and endothelial damage increased in the HFD and BCH groups. Cavernous smooth muscle to collagen ratio, nNOS and eNOS staining decreased significantly in the BIIAL, HFD, and BCH groups compared to the NC and MS groups.ConclusionsThe novel BCH model mimics the chronic pathophysiology of ED in humans and avoids the drawbacks of traditional ED models.

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“…Lee et al [57] showed that intracorporeal administration of brain-derived neurotrophic factors after bilateral cavernous nerve cryoablation in rats prevents the degeneration of neural nitric oxide synthase containing neurons, with an enhancement of recovery of erectile function. In addition, the intracorporeal injection of vascular endothelial growth factor in rats with arteriogenic erectile dysfunction can provide a protective effect on erectile function.…”

Section: Growth Factors For Cavernous Nerve Regenerationmentioning

confidence: 99%

Management of erectile dysfunction following radical prostatectomy

et al. 2001

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Radical prostatectomy is the standard treatment for organ/specimen-confined prostate cancer, yet erectile dysfunction in selected series is still reported as high as 90% after this procedure. Thus, most men need adjuvant treatments to be sexually active following radical prostatectomy. These include vacuum constriction devices, intracorporeal injections of vasoactive drugs, and transurethral dilators, all of which have reported response rates of 50% to 70%. Unfortunately, long-term compliance is suboptimal, with a discontinuation rate of nearly 50% at one year. These non-oral options should be offered on an individual basis to patients who have failed oral therapy since efficacy and compliance vary. Also, these options should be considered in the early postoperative period to enhance sexual activity and penile oxygenation, which may prevent corporeal fibrosis. Early penile rehabilitation with intracavernosal injections or vacuum constriction devices should be encouraged to increase chances for recovery of rigid erections. In patients with some preservation of nerve tissue, oral sildenafil may be effective in promoting an earlier return of erectile function. The potential impact of sildenafil and other new oral therapies should encourage urologists to continue to perform and perfect the nerve-sparing approach.

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The Effect of Vascular Endothelial Growth Factor on a Rat Model of Traumatic Arteriogenic Erectile Dysfunction

Abstract: Ligation of bilateral internal iliac arteries produced a reliable animal model of traumatic arteriogenic erectile dysfunction. Intracavernous injection of VEGF minutes after arterial ligation facilitated the recovery of erectile function.

Cited by 43 publications

References 31 publications

Designed angiopoietin-1 variant, COMP-angiopoietin-1, rescues erectile function through healthy cavernous angiogenesis in a hypercholesterolemic mouse

Designed angiopoietin-1 variant, COMP-angiopoietin-1, rescues erectile function through healthy cavernous angiogenesis in a hypercholesterolemic mouse

A Novel Method to Establish a Rat ED Model Using Internal Iliac Artery Ligation Combined with Hyperlipidemia

Management of erectile dysfunction following radical prostatectomy

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