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The pericyte as a cellular regulator of penile erection and a novel therapeutic target for erectile dysfunction.

ABSTRACT: Pericytes are known to play critical roles in vascular development and homeostasis. However, the distribution of cavernous pericytes and their roles in penile erection is unclear. Herein we report that the pericytes are abundantly distributed in microvessels of the subtunical area and dorsal nerve bundle of mice, followed by dorsal vein and cavernous sinusoids. We further confirmed the presence of pericytes in human corpus cavernosum tissue and successfully isolated pericytes from mouse penis. Cavernous pericyte contents from diabetic mice and tube formation of cultured pericytes in high glucose condition were greatly reduced compared with those in normal conditions. Suppression of pericyte function with anti-PDGFR-? blocking antibody deteriorated erectile function and tube formation in vivo and in vitro diabetic condition. In contrast, enhanced pericyte function with HGF protein restored cavernous pericyte content in diabetic mice, and significantly decreased cavernous permeability in diabetic mice and in pericytes-endothelial cell co-culture system, which induced significant recovery of erectile function. Overall, these findings showed the presence and distribution of pericytes in the penis of normal or pathologic condition and documented their role in the regulation of cavernous permeability and penile erection, which ultimately explore novel therapeutics of erectile dysfunction targeting pericyte function.

SUBMITTER: Yin GN

PROVIDER: S-EPMC4456662 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The pericyte as a cellular regulator of penile erection and a novel therapeutic target for erectile dysfunction.

Yin Guo Nan GN Das Nando Dulal ND Choi Min Ji MJ Song Kang-Moon KM Kwon Mi-Hye MH Ock Jiyeon J Limanjaya Anita A Ghatak Kalyan K Kim Woo Jean WJ Hyun Jae Seog JS Koh Gou Young GY Ryu Ji-Kan JK Suh Jun-Kyu JK

Scientific reports 20150605

Pericytes are known to play critical roles in vascular development and homeostasis. However, the distribution of cavernous pericytes and their roles in penile erection is unclear. Herein we report that the pericytes are abundantly distributed in microvessels of the subtunical area and dorsal nerve bundle of mice, followed by dorsal vein and cavernous sinusoids. We further confirmed the presence of pericytes in human corpus cavernosum tissue and successfully isolated pericytes from mouse penis. C ...[more]

PMID: 26044953

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Project description:Background: Neuroimaging studies have demonstrated that the prefrontal cortex and amygdala play an important role in sexual arousal (SA). However, little is known about the interactions between the prefrontal and cortex amygdala, which mediate the cognitive regulation of emotion and SA. Objective: We seek to determine whether nocturnal erection of psychogenic erectile dysfunction (pED) patients are normal and whether there are changes of topological organization in the prefrontal-amygdala pathway of brain network in pED. In addition, whether there are correlations between network property changes and self-reported emotion and erection. Design, setting, and participants: We used the RigiScan device to evaluate erectile function of patients and employed diffusion MRI and graph theory to construct brain networks of 21 pED patients and 24 healthy controls. Outcome measurements and statistical analysis: We considered four nodal metrics and their asymmetry scores, and nocturnal penile tumescence (NPT) parameters, to evaluate the topological properties of brain networks of pED and their relationships with the impaired self-reported emotion and erection. Results and limitations: All the pED patients showed normal nocturnal penile erection, however impaired self-reported erection and negative emotion. In addition, patients showed lower connectivity degree and strength in the left prefrontal-amygdala pathway. We also found that pED exhibited lower leftward asymmetry in the inferior frontal gyrus. Furthermore, patients showed more hub regions and fewer pivotal connections. Moreover, the degree of the left amygdala of pED showed significantly negative correlation with the self-reported erection and positive correlation with the self-reported negative emotion. Conclusions: Together, these results suggest normal nocturnal erection in pED. However, abnormalities of brain network organization in pED, particularly in the left prefrontal-amygdala pathway, are associated with the impaired self-reported erection and negative emotion.

Project description:Patients complaining of short penile length pose a challenge in urology practice. Those men who present seeking penile lengthening surgery usually overestimate 'normal' penile length, and may in often cases relate their penile length with the degree of masculinity and self-esteem. Penile prosthetic devices are the gold standard treatment of erectile dysfunction (ED) after failure of conservative options. Penile shortening is the most prevalent long-term complaint after successful inflatable penile prosthesis (IPP) placement. This has a significant impact on patient's overall satisfaction and quality of life. Using PubMed, we performed a thorough literature review of the current procedures of preservation or enhancement of penile length as well as reported perioperative protocols in patients undergoing penile prosthesis (PP) insertion. Keywords used were "penile lengthening", "penile enhancement", "penile girth", "inflatable penile prosthesis" and "glans augmentation". Several surgical techniques can be offered in the setting of penile shortening concurrently with PP insertion, e.g., sub-coronal approach of PP placement, sliding technique, modified sliding technique (MoST), multiple-slide technique (MuST), and tunica mesh expansion procedure (TMEP). Adjuvant techniques can also improve subjective penile length include, ventral phalloplasty, suprapubic lipectomy, suspensory ligament release and use of expanding penile implants. Preoperative protocols including use of a vacuum erectile device, traction therapy also seem to improve postoperative outcomes, minimizing postoperative pain, and encouraging the early device use. Currently, there is no consensus among experts on a particular lengthening procedure or when they can be performed to optimize outcomes. Furthermore, it is imperative to set proper expectations before surgery, with extensive patient and partner counseling. When used in the properly selected patient, penile lengthening procedures show promising results with minimal complication rates.

Project description:Penile echo-color Doppler ultrasound (PCDU) is the gold standard for the diagnosis of arterial erectile dysfunction (ED). Its reliability in patients with anxiety was questioned, due to false-positive results. To assess the penile hemodynamic response to intracavernous injection (ICI) of alprostadil in patients with anxiety-related ED. Patients with non-organic ED and a 5-item International Index of Erectile Function (IIEF-5) score ranging between 5 and 7 were enrolled. They were asked to compile the 7-item Generalized Anxiety Disorder (GAD-7) questionnaire to assess the degree of anxiety and were divided according to the GAD-7 score in Group 1 with minimal level of anxiety (n = 20), Group 2 with mild anxiety (n = 20), Group 3 with moderate anxiety (n = 20), and Group 4 with severe anxiety (n = 20). Peak systolic velocity (PSV) and the end-diastolic velocity (EDV) were sampled in all patients, through PCDU in the flaccid state, and 5, 10, 15, and 20 min after ICI of alprostadil at the standard dose of 10 μg. In penile flaccidity, the patients showed a mean PSV of 8.0 ± 4.0 cm/s. The degree of anxiety was found to significantly influence both PSV and EDV at all assessed time-points. Particularly, it was negatively associated with the PSV at time 5 (r = -0.9, p < 0.01), 10 (r = -0.9, p < 0.01), 15 (r = -0.9, p < 0.01), and 20 (r = -0.7, p < 0.01) minutes, and positively with the EDV at time 5 (r = 0.7, p < 0.01), 10 (r = 0.6, p < 0.01), 15 (r = 0.5, p < 0.01), and 20 (r = 0.3, p < 0.01) minutes. Although all patients showed a mean dynamic PSV > 25 cm/s (which excluded an arterial ED according to the current guidelines), a peculiar hemodynamic pattern was found in patients with severe anxiety. In these patients, normal PSV values were reached only after 20 min from ICI, suggesting a "late-responder" profile. If further studies confirm the existence of a distinct hemodynamic profile in patients with severe anxiety, sampling the PSV and the EDV values could be proposed, for detecting patients with severe anxiety-related ED. Dynamic PCDU could be considered an accurate diagnostic test in patients with non-organic ED, since zero false-positive results were found in the present study. PSV in the flaccid state is not able to discriminate between arterial- or non-organic ED.

Project description:ObjectiveTo investigate the rate of erectile dysfunction (ED) after pelvic ring fracture (PRF).DesignSystematic review and meta-analysis.MethodsA systematic literature search of the Cochrane, EMBASE, MEDLINE, Scopus and Web of Science Library databases was conducted in January 2020. Included were original studies performed on humans assessing ED after PRF according to the 5-item International Index of Erectile Function (IIEF-5) questionnaire and fracture classification following Young and Burgess, Tile or Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association. Furthermore, interventional cohort studies assessing the effect of penile rehabilitation therapy with phosphodiesterase-5-inhibitors (PDE-5-I) on IIEF-5 scores compared before and after treatment were included. Results were presented as forest plots of proportions of patients with ED after PRF or mean changes on IIEF-5 questionnaires before and after penile rehabilitation. Studies not included in the quantitative analysis were narratively summarised. Risk of bias assessment was conducted using the revised tool for the Quality Assessment on Diagnostic Accuracy Studies.ResultsThe systematic literature search retrieved 617 articles. Seven articles were included in the qualitative analysis and the meta-analysis. Pooled proportions revealed 37% of patients with ED after suffering any form of PRF (result on probability scale pr=0.37, 95% CI: 0.26 to 0.50). Patients after 3 months of penile rehabilitation therapy reported a higher IIEF-5 score than before (change score=6.5 points, 95% CI: 2.54 to 10.46, p value=0.0013).ConclusionDespite some heterogeneity and limited high-quality research, this study concludes that patients suffering from any type of PRF have an increased risk of developing ED. Oral intake of PDE-5-I for the purpose of penile rehabilitation therapy increases IIEF-5 scores and may relevantly influence quality-of-life in these patients.Prospero registration numberCRD42020169699.

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The pericyte as a cellular regulator of penile erection and a novel therapeutic target for erectile dysfunction.

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The pericyte as a cellular regulator of penile erection and a novel therapeutic target for erectile dysfunction.

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