Phosphodiesterase type 5 in men with vasculogenic and post‐radical prostatectomy erectile dysfunction: is there a molecular difference?

Karakus, Serkan; Musicki, Biljana; Burnett, Arthur L.

doi:10.1111/bju.14433

Cited by 12 publications

(9 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, molecular analysis of protein expression showed significant changes of neuronal proteins in post-RP ED which differs from that observed in vasculogenic ED. 16 In line to what is observed in humans, it was reported that penile endothelial function was preserved in rats after crushing of the CNs. 18 , 19 In contrast, imbalanced neurogenic responses favoring adrenergic contraction over nitrergic relaxations have been observed in the human tissue and rat model.…”

Section: Introductionsupporting

confidence: 62%

“… 15 It has been shown that ED occurring after RP differs from classical vasculogenic ED. 16 , 17 , 18 , 19 In human corpus cavernosum tissue, endothelial function was preserved in patients after RP, whereas significant disturbances were seen in neurogenic relaxation with sympathetic hyper innervation. Accordingly, molecular analysis of protein expression showed significant changes of neuronal proteins in post-RP ED which differs from that observed in vasculogenic ED.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

European Society for Sexual Medicine Consensus Statement on the Use of the Cavernous Nerve Injury Rodent Model to Study Postradical Prostatectomy Erectile Dysfunction

et al. 2020

View full text Add to dashboard Cite

Introduction Rodent animal models are currently the most used in vivo model in translational studies looking into the pathophysiology of erectile dysfunction after nerve-sparing radical prostatectomy. Aim This European Society for Sexual Medicine (ESSM) statement aims to guide scientists toward utilization of the rodent model in an appropriate, timely, and proficient fashion. Methods MEDLINE and EMBASE databases were searched for basic science studies, using a rodent animal model, looking into the consequence of pelvic nerve injury on erectile function. Main outcome measures The authors present a consensus on how to best perform experiments with this rodent model, the details of the technique, and highlight possible pitfalls. Results Owing to the specific issue—basic science—Oxford 2011 Levels of Evidence criteria cannot be applied. However, ESSM statements on this topic will be provided in which we summarize the ESSM position on various aspects of the model such as the use of the Animal Research Reporting In Vivo Experiments guideline and the of common range parameter for nerve stimulation. We also highlighted the translational limits of the model. Conclusion The following statements were formulated as a suggestive guidance for scientists using the cavernous nerve injury model. With this, we hope to standardize and further improve the quality of research in this field. It must be noted that this model has its limitations. Weyne E, Ilg MM, Cakir OO, et al. European Society for Sexual Medicine Consensus Statement on the Use of the Cavernous Nerve Injury Rodent Model to Study Postradical Prostatectomy Erectile Dysfunction. Sex Med 2020;8:327–337.

show abstract

Section: Introductionsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

European Society for Sexual Medicine Consensus Statement on the Use of the Cavernous Nerve Injury Rodent Model to Study Postradical Prostatectomy Erectile Dysfunction

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Among the included articles, five articles describe the role of Rho-kinase in ED pathogenesis using various models including cavernous nerve (CN) crush injury, heart failure (HF)-induced ED, Vasculogenic and post-radical prostatectomy (RP) ED, diabetes-induced ED and age-related ED. 17 , 33 , 36 Ten papers describe the role of novel drugs which have been tested for the treatment of ED by targeting Rho-kinase as a potential therapy for ED. 19 , 20 , 37 , 45 The remaining three papers describe the role of traditionally claimed plants for the treatment of ED and evaluated for their potential role in targeting Rho-kinase in animal models.…”

Section: Resultsmentioning

confidence: 99%

“… Post-RP ED was characterized by decreased eNOS protein expression, increased eNOS phosphorylation on its activator site (Ser-1412), uncoupled eNOS, down-regulated PDE5 protein expression, and increased oxidative stress in erectile tissue. 36 Abbreviations: CN, cavernous nerve; DM, diabetes mellitus; ED, erectile dysfunction; eNOS, endothelial nitric-oxide synthase; ICP, intracavernosal pressure; MAP, mean arterial pressure; MLCK, myosin light chain kinase; MLCP, myosin light chain phosphatase; ROCK, Rho-associated coiled-coil-forming protein kinase. …”

Section: Resultsmentioning

confidence: 99%

<p>A Systematic Review on Rho-Kinase as a Potential Therapeutic Target for the Treatment of Erectile Dysfunction</p>

Zewdie

Ayza

Tesfaye

et al. 2020

RRU

View full text Add to dashboard Cite

Background: Erectile dysfunction (ED) is a common clinical condition with limited treatment options. The main aim of the present systematic review was to synthesize information on Rho-kinase as a novel therapeutic approach for the treatment of ED. Methods: We performed a systematic literature study in PubMed, Google Scholar and Scopus. Included studies were original articles studied the role of Rho-kinase in the pathogenesis and/or new treatment approach for ED in animal models and clinical studies, published between 2014 and 2019. Data derived from each study were study design used, interventions applied and main treatment outcomes. The quality of the selected articles was assessed by CAMARADES criteria and data were analyzed using descriptive statistics. Results: A total of 1067 original articles were retrieved in the given period and eighteen papers met our inclusion criteria. Five articles explain the role of Rho-kinase in ED pathogenesis using different models such as cavernous nerve crush injury, heart failureinduced ED, vasculogenic and post-radical prostatectomy ED, diabetes-induced ED and agerelated ED. Other ten papers explain the role of novel drugs evaluated for ED treatment by targeting Rho-kinase as a new approach for ED therapy. The rest three papers discuss the role of plant extracts used by traditional society for the treatment of ED and assess their potential function in targeting Rho-kinase in animal models. The penile erectile functional index has shown that the ratio of intracavernosal pressure to mean arterial pressure (ICP/MAP) was decreased due to age and various chronic diseases. Whilst, ROCK I and ROCK II expression were increased. Western blot findings have also shown that ROCK II and MYPT-1 phosphorylation rates increased in cavernous tissue after ED induction. Besides, compounds which can inhibit the action of Rho-kinase activity showed relaxation of the corpus cavernosum, decrease in corporal fibrosis, and alleviate increased apoptosis and caspase-3 activity in an NO-independent manner. Moreover, histological and molecular dysregulation have been improved by inhibition of Rho-kinase. Conclusion: Targeting Rho-kinase may be a possible target for the treatment of ED secondary to specific causes, and Rho-kinase inhibitors may be a new drug family for the treatment of ED. However, this requires further studies for in-depth understanding.

show abstract

“…Although the causes of post-RP ED are considered to be multifactorial (neurogenic due to nerve injury, arteriogenic due to vascular injury, venogenic, or a combination thereof), structural alterations in the corpus cavernosum induced by CN injury during RP are known to be the main causes of post-RP. 2,3,19,20 Previously, we showed that the upregulation of JNK and LIMK2 pathways from the early post-injury period in a rat model of CNCI played a critical role in cavernosal apoptosis and fibrosis, respectively. 13,21 On the basis of these results, our recent study tested if the dual inhibition of JNK and LIMK2 would normalize erectile function by suppressing both cavernosal apoptosis and fibrosis in a rat model of CNCI.…”

Section: Discussionmentioning

confidence: 99%

Restoration of erectile function by a combination of antiapoptosis by JNK inhibitor and preservation of smooth muscle or endothelium by hepatocyte growth factor in a rat model of cavernous nerve injury

Kim

Lee

et al. 2021

The Prostate

View full text Add to dashboard Cite

Background: Because of structural alterations in the corpus cavernosum after radical prostatectomy (RP), post-RP erectile dysfunction remains a very difficult condition to treat. We aimed to determine if the combined administration of a Jun-amino terminal kinase (JNK) inhibitor and hepatocyte growth factor (HGF) in the immediate post-injury period would restore erectile function by antiapoptotic and proregenerative effects through the rectification of molecular pathways related to the structural integrity of the penis in a rat model of bilateral cavernosal nerve crush injury (CNCI).Methods: A total of 70 rats were divided into five groups: Sham surgery (S), CNCI (I), and once-daily intraperitoneal administration of 10.0 mg/kg JNK inhibitor + twiceweekly intracavernosal administration of low-dose (2.1 μg), medium-dose (4.2 μg), or high-dose (8.4 μg) HGF (I + J + LH or I + J + MH or I + J + HH, respectively) in the immediate post-injury period. Erectile responses to electrostimulation (1.0, 3.0, and 5.0 V), histological staining, caspase-3 activity, and Western blotting were evaluated 9 days after surgery.Results: Group I showed lower intracavernosal pressure (ICP)/mean arterial pressure (MAP) after stimulation at each voltage, lower area under the curve (AUC)/MAP after stimulation at each voltage, less smooth muscle (SM) content, a lower SM/ collagen ratio, higher caspase-3 activity, increased cJun phosphorylation, decreased protein expression of PECAM-1, decreased cMet phosphorylation, and decreased endothelial nitric oxide synthase (eNOS) phosphorylation compared to Group S. The SM content, SM/collagen ratio, protein expression of ICP/MAP, or AUC/MAP after stimulation at each voltage in Group I + J + LH were partially restored, despite the normalization of cJun phosphorylation and caspase-3 activity. The ICP/MAP, AUC/MAP, caspase-3 activity, SM content, protein expression of PECAM-1, cJun phosphorylation, cMet phosphorylation, and eNOS phosphorylation in both Groups I + J + MH and I + J + HH were restored to the levels observed in Group S, while the SM/collagen ratio was significantly improved but not completely normalized.

show abstract

Phosphodiesterase type 5 in men with vasculogenic and post‐radical prostatectomy erectile dysfunction: is there a molecular difference?

Cited by 12 publications

References 33 publications

European Society for Sexual Medicine Consensus Statement on the Use of the Cavernous Nerve Injury Rodent Model to Study Postradical Prostatectomy Erectile Dysfunction

European Society for Sexual Medicine Consensus Statement on the Use of the Cavernous Nerve Injury Rodent Model to Study Postradical Prostatectomy Erectile Dysfunction

<p>A Systematic Review on Rho-Kinase as a Potential Therapeutic Target for the Treatment of Erectile Dysfunction</p>

Restoration of erectile function by a combination of antiapoptosis by JNK inhibitor and preservation of smooth muscle or endothelium by hepatocyte growth factor in a rat model of cavernous nerve injury

Contact Info

Product

Resources

About