To determine the prevalence of erectile dysfunction (ED) in metabolically healthy obese (MHO) ind... more To determine the prevalence of erectile dysfunction (ED) in metabolically healthy obese (MHO) individuals, and to compare ED severity and hypogonadism prevalence in MHO, metabolically unhealthy obese (MUO) and metabolically healthy non-obese individuals. ED patients (n=460) were evaluated by standardized protocol, that included clinical evaluation, abridged 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire survey, and Penile Duplex Doppler Ultrasound (PDDU) exam. Patients were classified as obese [body mass index (BMI) ≥30.0 kg/m] and non-obese (BMI <30.0 kg/m), and metabolic health status was defined by National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) criteria. Statistical analysis was performed and statistical significance was considered at p-level <0.05. The mean age of the subjects was 56.2±10.5 years. MHO was present in 40% of obese individuals (n=37). MUO had lower mean peak systolic velocity (mPSV) compar...
Textbook of Male Genitourethral Reconstruction, 2019
In this chapter the surgical treatment of erectile dysfunction and its historical perspective are... more In this chapter the surgical treatment of erectile dysfunction and its historical perspective are reviewed. The standard surgical treatment of erectile dysfunction is the implantation of a penile prothesis, either semirigid or inflatable ones. Penile prothesis materials and design have improved along the last three decades, contributing to a lower rate of mechanical complications and an increased long-term durability. Both penile prothesis hydrophilic- and antibiotic impregnated-coatings, as well as new operative approaches such as the “no touch” approach, have greatly contributed to the lower rate of post-operative infection observed in recent years. Surgeons must be aware of both intra- and post-operative complications of penile prothesis implantation and their management as its prevention is key to success. Penile revascularization still has a minor role in the surgical treatment of erectile dysfunction, although patient selection is key.
The prevention of HPV-related diseases is an important healthcare issue due to its increasing inc... more The prevention of HPV-related diseases is an important healthcare issue due to its increasing incidence. Primary prevention is most important in males as it avoids initial infection and includes the use of condom, circumcision and vaccination. Primary prevention with vaccination is effective in decreasing HPV-related lesions in women up to 45 years old and the existing data for men comes from the experience from vaccinating women. Although it is the only vaccine that prevents cancer, the worldwide rates of vaccination in males is very low due to lack of information related to efficacy and side effects, lack of recommendation from the treating doctor, price and concern about encouragement of sexual promiscuity.
Cardiovascular disease risk factors (CVDRF), especially diabetes mellitus (DM), disrupt oxidative... more Cardiovascular disease risk factors (CVDRF), especially diabetes mellitus (DM), disrupt oxidative stress response. This condition underlies endothelial dysfunction, early manifested in men as erectile dysfunction. The current study is aimed at elucidating the impact of CVDRF in the oxidation responsive AMPK/SIRT1-PGC-1α-SIRT3 pathway and related miRNAs in the human corpus cavernosum. Human penile tissue fragments from individuals submitted to programmed urological surgeries (n=27), aged 43-63 years, were clustered depending on the presence of CVDRF; the control group included samples from patients without CVDRF, and groups A and B included samples from patients with DM and additional CVDRF, totalizing ≤2 CVDRF (group A) and ≥3 CVDRF (group B). Dual-immunolabelling of SIRT3, SOD2, or GPX1 with α-actin in tissue sections was carried out. The assessment of expression levels of NOX1, phospho-AMPKα, total AMPKα, SIRT1, PGC-1α, SIRT3, SOD2, and GPX1 was performed by western blotting and o...
Phalloplasty can be either performed as a penile reconstructive or phallic constructive procedure... more Phalloplasty can be either performed as a penile reconstructive or phallic constructive procedure, mainly in penile trauma victims or female-to-male gender reassignment. After the introduction of the radial artery-based forearm free flap and with the further awareness of patient desire to void while standing, urethral reconstruction became a standard procedure and a main goal to attain in phalloplasty. Urethroplasty techniques can be broadly split in two main groups: as part of a tube-within-a-tube skin flap or as an independent other-than-skin graft. Urethral complications, such as fistula, stricture, or stones, are common and often recur after treatment. In this review, the main techniques of urethral reconstruction in phalloplasty are reviewed and compared. Urethral complications are also reviewed as well as their management.
Introduction: Erectile dysfunction (ED) is one of the most prevalent male sexual disorders worldw... more Introduction: Erectile dysfunction (ED) is one of the most prevalent male sexual disorders worldwide. When conservative treatment is unsuccessful, contraindicated or causes unacceptable side effects penile prosthesis implantation is a definitive option for the management of ED. Although considered a third-line therapy, it achieves the highest satisfaction rates as compared with non-surgical treatment. Three-piece inflatable penile prothesis (IPP) represents the most sophisticated implantable device, AMS 700CX TM and Coloplast Titan ® being the two most commonly used. Although there are several studies evaluating patient satisfaction with either model, there is little published data comparing both models. Methods: We have compared overall patient satisfaction in 55 patients submitted to either 700CX TM or Titan ® implantation. The Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire was used to access patient satisfaction. Results: Patient mean age and follow-up time were 59.1 years and 57.9 months respectively. There was no difference in EDITS score between 700CX TM and Titan ® IPP (77.2 ± 12.1 versus 77.5 ± 16.6 respectively, p = 0.956). Conclusion: Overall patient satisfaction as assessed by EDITS questionnaire was not different between 700CX TM and Titan ® .
To evaluate surgical outcomes and complications and assess overall patient satisfaction after sma... more To evaluate surgical outcomes and complications and assess overall patient satisfaction after small intestinal submucosa (SIS) grafting for Peyronie disease. Twenty-eight patients were treated with tunical incision and grafting with SIS. Mean age of the patients was 58 (range: 43-71) years. A preoperative protocol was applied to all patients. Patients were also evaluated at follow-up clinic visits. The International Index of Erectile Function, a modified Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire, postoperative self-reports, and clinical characteristics were used to measure outcomes. Hypertension, hypercholesterolemia, and type 2 diabetes were reported in 53,6%, 46,4%, and 28,6% of patients, respectively. Previous penile trauma was reported by 10,7%. The mean operative time was 151 ± 23 minutes. Average follow-up was 18 months (range: 3-36). The only surgical complication was 1 case of infected hematoma treated with surgical drainage. Self-reported complete resolution of curvature was 82,1%. Subjective perception of penile shortening was reported by 71,4% of patients. However, only 4 patients objectively showed postoperative penile shortening. Erectile function was completely preserved in 64,2%. Four patients complained of erectile dysfunction despite medication, even though no objective vascular etiology was shown on postoperative penile Doppler ultrasound. Overall, 82,2% of patients reported high levels of satisfaction. Surgical treatment of Peyronie disease using SIS grafting is a safe option, with low rate of major complications. It has good surgical outcomes and high patient satisfaction rates.
primary hypogonadal men were the least healthy (CCI defined) group, having higher BMI, waist circ... more primary hypogonadal men were the least healthy (CCI defined) group, having higher BMI, waist circumference, IPSS score, and lower IIEF sexual desire score (all p<0.03). Overall, health status, waist circumference, BMI, and CCI worsened according to the defined gonadal status, with a less favorable profile in primary and secondary hypogonadal men as compared to compensated ones (all p<0.01). Among IIEF domains, sexual desire was the only one negatively influenced by the gonadal status (p¼0.03); conversely, erectile function domain did not vary significantly among the analyzed groups. Interestingly, LUTS severity (as for IPSS scores) worsened according to the gonadal status (p¼0.01). CONCLUSIONS: Overall, the prevalence of TD was 23.6% within our cohort of Caucasian-European men presenting for new-onset ED. Clinical, endocrine and metabolic characteristics significantly worsen according to the defined gonadal status.
INTRODUCTION AND OBJECTIVES: Tissue morcellation is an important step during Holmium laser enucle... more INTRODUCTION AND OBJECTIVES: Tissue morcellation is an important step during Holmium laser enucleation of the prostate (HoLEP). This study compares the efficiency of the new VersaCut TM + tissue morcellation system and the older VersaCut TM tissue morcellator system. METHODS: The first 20 patients who underwent HoLEP and tissue morcellation using the new VersaCut TM tissue morcellation system at our institute were included in this study (group1). These patients were matched based on the enucleated tissue weight to patients from our prospectively maintained HoLEP database (group 2) with a 2:1 matching ratio. Peri-operative characteristics, operative times, morcellation times and complications were reported and compared between the two groups. Morcellation efficiency (defined as the weight of morcellated tissue per morcellation time) was calculated and compared between the two groups. RESULTS: The preoperative prostate volume was not different between the two groups [96.9 gm (SD 42) for group 1 vs 97.3 gm (SD 39.8) for group 2, (p¼ 0.967)]. There were no differences in the enucleated weight between the two groups [51.2 gm (SD 26.3) for group 1 vs 50.7gm (SD25.9) for group 2, (p¼0.949)]. Total operative times were not different between the two groups [123.5 minutes (SD 44.1) for group 1 and 152 minutes (SD 55.4) for group 2, p¼ 0.781). When the new morcellator was used, mean morcellation time was 19.9 minuts (SD13.7) whereas mean morcellation time was 14.6 minutes (SD11.6) with the older morcellator (p¼0.122). Morcellation efficiency was comparable between the two groups [3.33 gm/minute (SD1.82) for group 1 vs 4.44 gm/minute (SD 2.45) for group 2]. There were no complications in both groups. When the morcellated tissue was examined postoperatively, there were no differences in the incidence of prostatitis or prostate cancer in the two groups. CONCLUSIONS: When matched by the resected prostatic tissue weight, there were no differences identified in the efficiency of the old VaersaCut TM and the new VersaCut+ TM morcellation systems.
To evaluate the expression of the angiogenic factors vascular endothelial growth factor (VEGF) an... more To evaluate the expression of the angiogenic factors vascular endothelial growth factor (VEGF) and angiopoietins (Ang) 1 and 2, in normal human penile erectile tissue. Penile fragments were removed from four young healthy organ donors (aged 17-28 years), and processed for immunohistochemical studies for VEGF, Ang1 and Ang2, and their specific receptors (VEGFR1 and 2, and Tie2, respectively). Molecular analysis was used to confirm the expression of VEGF and Angs in erectile tissue. VEGF and VEGFR1 expression was restricted to smooth muscle cells (SMCs). VEGFR2 was detected mainly in the endothelium lining and to a lesser extent in the SMC. Ang1 had a scattered distribution mostly in the perivascular SM layer, showing co-localization with VEGF. Tie2 was faintly detected in the endothelial cells. Ang2 was not detected by immunohistochemical studies, but the use of the same antibody in molecular analysis confirmed Ang2 expression in human corpus cavernosum. We show for the first time the co-localization of VEGF and Ang1 in the SMC, suggesting an interaction for vessel stabilization. Ang2 seems to be available for neoangiogenesis, if challenged. Studies of endothelial markers, growth factors and specific receptors are useful for understanding vascular organization and angiogenesis in normal human erectile tissue. This knowledge will be fundamental for developing newer therapeutic approaches to prevent or even cure erectile dysfunction.
Sirtuin (SIRT)1 was recently identified in human corpus cavernosum (CC). We hypothesized that oth... more Sirtuin (SIRT)1 was recently identified in human corpus cavernosum (CC). We hypothesized that other sirtuins could also be expressed in the CC. Expression of these enzymes in tissues is affected by aging, the main independent risk factor for erectile dysfunction besides other cardiovascular disease risk factors (CVDRF), such as diabetes or obesity. The aim of this study was to characterize the expression of SIRT1-3 and SIRT5-7 in human CC relatively to age and CVDRF. Samples of CC collected from patients submitted to programmed surgeries or organ donors were divided in three groups according to age and presence of CVDRF. Expression of SIRT1-3 and SIRT5-7 mRNAs was assessed by real-time polymerase chain reaction. Cellular localization and semi-quantification of sirtuins proteins were performed by immunofluorescence and Western blotting (WB), respectively. Nuclear factor kappa B (NFkB)-p65, inducible (iNOS) and endothelial nitric oxide synthase (eNOS) levels were also assayed by WB. The main outcome measure was to characterize the expression of SIRT1-3 and SIRT5-7 in human CC. SIRT1-3 and SIRT5-7 mRNAs were detected in all individuals, without statistical differences among groups, excepting SIRT7 that decreased four times in aged groups relatively to young (P = 0.013). WB analysis demonstrated that aged individuals with CVDRF presented higher levels of SIRT7 protein relatively to young (P = 0.0495) and lower levels of SIRT3 protein relatively to healthy aged (P = 0.0077). Expression of NFkB-p65 and iNOS were higher in aged than in young individuals (P = 0.0185; P = 0.004, respectively). No differences in other sirtuins or total eNOS were seen among groups although phospho eNOS Ser(1177) levels decreased in groups of aged men relatively to young (P = 0.0043; P = 0.0099). Our results demonstrate for the first time expression of SIRT2-3 and SIRT5-7 in the human CC. Aged individuals with CVDRF presented an increase in SIRT7 protein levels and a decrease in mitochondrial SIRT3. This finding suggests that CVDRF induces the loss of antioxidant defense mechanisms leading to endothelial injury. Freitas M, Rodrigues AR, Tomada N, Fonseca J, Magalhães A, Gouveia AM, Neves D. Effects of aging and cardiovascular disease risk factors on the expression of sirtuins in the human corpus cavernosum. J Sex Med **;**:**-**.
To determine the prevalence of erectile dysfunction (ED) in metabolically healthy obese (MHO) ind... more To determine the prevalence of erectile dysfunction (ED) in metabolically healthy obese (MHO) individuals, and to compare ED severity and hypogonadism prevalence in MHO, metabolically unhealthy obese (MUO) and metabolically healthy non-obese individuals. ED patients (n=460) were evaluated by standardized protocol, that included clinical evaluation, abridged 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire survey, and Penile Duplex Doppler Ultrasound (PDDU) exam. Patients were classified as obese [body mass index (BMI) ≥30.0 kg/m] and non-obese (BMI <30.0 kg/m), and metabolic health status was defined by National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) criteria. Statistical analysis was performed and statistical significance was considered at p-level <0.05. The mean age of the subjects was 56.2±10.5 years. MHO was present in 40% of obese individuals (n=37). MUO had lower mean peak systolic velocity (mPSV) compar...
Textbook of Male Genitourethral Reconstruction, 2019
In this chapter the surgical treatment of erectile dysfunction and its historical perspective are... more In this chapter the surgical treatment of erectile dysfunction and its historical perspective are reviewed. The standard surgical treatment of erectile dysfunction is the implantation of a penile prothesis, either semirigid or inflatable ones. Penile prothesis materials and design have improved along the last three decades, contributing to a lower rate of mechanical complications and an increased long-term durability. Both penile prothesis hydrophilic- and antibiotic impregnated-coatings, as well as new operative approaches such as the “no touch” approach, have greatly contributed to the lower rate of post-operative infection observed in recent years. Surgeons must be aware of both intra- and post-operative complications of penile prothesis implantation and their management as its prevention is key to success. Penile revascularization still has a minor role in the surgical treatment of erectile dysfunction, although patient selection is key.
The prevention of HPV-related diseases is an important healthcare issue due to its increasing inc... more The prevention of HPV-related diseases is an important healthcare issue due to its increasing incidence. Primary prevention is most important in males as it avoids initial infection and includes the use of condom, circumcision and vaccination. Primary prevention with vaccination is effective in decreasing HPV-related lesions in women up to 45 years old and the existing data for men comes from the experience from vaccinating women. Although it is the only vaccine that prevents cancer, the worldwide rates of vaccination in males is very low due to lack of information related to efficacy and side effects, lack of recommendation from the treating doctor, price and concern about encouragement of sexual promiscuity.
Cardiovascular disease risk factors (CVDRF), especially diabetes mellitus (DM), disrupt oxidative... more Cardiovascular disease risk factors (CVDRF), especially diabetes mellitus (DM), disrupt oxidative stress response. This condition underlies endothelial dysfunction, early manifested in men as erectile dysfunction. The current study is aimed at elucidating the impact of CVDRF in the oxidation responsive AMPK/SIRT1-PGC-1α-SIRT3 pathway and related miRNAs in the human corpus cavernosum. Human penile tissue fragments from individuals submitted to programmed urological surgeries (n=27), aged 43-63 years, were clustered depending on the presence of CVDRF; the control group included samples from patients without CVDRF, and groups A and B included samples from patients with DM and additional CVDRF, totalizing ≤2 CVDRF (group A) and ≥3 CVDRF (group B). Dual-immunolabelling of SIRT3, SOD2, or GPX1 with α-actin in tissue sections was carried out. The assessment of expression levels of NOX1, phospho-AMPKα, total AMPKα, SIRT1, PGC-1α, SIRT3, SOD2, and GPX1 was performed by western blotting and o...
Phalloplasty can be either performed as a penile reconstructive or phallic constructive procedure... more Phalloplasty can be either performed as a penile reconstructive or phallic constructive procedure, mainly in penile trauma victims or female-to-male gender reassignment. After the introduction of the radial artery-based forearm free flap and with the further awareness of patient desire to void while standing, urethral reconstruction became a standard procedure and a main goal to attain in phalloplasty. Urethroplasty techniques can be broadly split in two main groups: as part of a tube-within-a-tube skin flap or as an independent other-than-skin graft. Urethral complications, such as fistula, stricture, or stones, are common and often recur after treatment. In this review, the main techniques of urethral reconstruction in phalloplasty are reviewed and compared. Urethral complications are also reviewed as well as their management.
Introduction: Erectile dysfunction (ED) is one of the most prevalent male sexual disorders worldw... more Introduction: Erectile dysfunction (ED) is one of the most prevalent male sexual disorders worldwide. When conservative treatment is unsuccessful, contraindicated or causes unacceptable side effects penile prosthesis implantation is a definitive option for the management of ED. Although considered a third-line therapy, it achieves the highest satisfaction rates as compared with non-surgical treatment. Three-piece inflatable penile prothesis (IPP) represents the most sophisticated implantable device, AMS 700CX TM and Coloplast Titan ® being the two most commonly used. Although there are several studies evaluating patient satisfaction with either model, there is little published data comparing both models. Methods: We have compared overall patient satisfaction in 55 patients submitted to either 700CX TM or Titan ® implantation. The Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire was used to access patient satisfaction. Results: Patient mean age and follow-up time were 59.1 years and 57.9 months respectively. There was no difference in EDITS score between 700CX TM and Titan ® IPP (77.2 ± 12.1 versus 77.5 ± 16.6 respectively, p = 0.956). Conclusion: Overall patient satisfaction as assessed by EDITS questionnaire was not different between 700CX TM and Titan ® .
To evaluate surgical outcomes and complications and assess overall patient satisfaction after sma... more To evaluate surgical outcomes and complications and assess overall patient satisfaction after small intestinal submucosa (SIS) grafting for Peyronie disease. Twenty-eight patients were treated with tunical incision and grafting with SIS. Mean age of the patients was 58 (range: 43-71) years. A preoperative protocol was applied to all patients. Patients were also evaluated at follow-up clinic visits. The International Index of Erectile Function, a modified Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire, postoperative self-reports, and clinical characteristics were used to measure outcomes. Hypertension, hypercholesterolemia, and type 2 diabetes were reported in 53,6%, 46,4%, and 28,6% of patients, respectively. Previous penile trauma was reported by 10,7%. The mean operative time was 151 ± 23 minutes. Average follow-up was 18 months (range: 3-36). The only surgical complication was 1 case of infected hematoma treated with surgical drainage. Self-reported complete resolution of curvature was 82,1%. Subjective perception of penile shortening was reported by 71,4% of patients. However, only 4 patients objectively showed postoperative penile shortening. Erectile function was completely preserved in 64,2%. Four patients complained of erectile dysfunction despite medication, even though no objective vascular etiology was shown on postoperative penile Doppler ultrasound. Overall, 82,2% of patients reported high levels of satisfaction. Surgical treatment of Peyronie disease using SIS grafting is a safe option, with low rate of major complications. It has good surgical outcomes and high patient satisfaction rates.
primary hypogonadal men were the least healthy (CCI defined) group, having higher BMI, waist circ... more primary hypogonadal men were the least healthy (CCI defined) group, having higher BMI, waist circumference, IPSS score, and lower IIEF sexual desire score (all p<0.03). Overall, health status, waist circumference, BMI, and CCI worsened according to the defined gonadal status, with a less favorable profile in primary and secondary hypogonadal men as compared to compensated ones (all p<0.01). Among IIEF domains, sexual desire was the only one negatively influenced by the gonadal status (p¼0.03); conversely, erectile function domain did not vary significantly among the analyzed groups. Interestingly, LUTS severity (as for IPSS scores) worsened according to the gonadal status (p¼0.01). CONCLUSIONS: Overall, the prevalence of TD was 23.6% within our cohort of Caucasian-European men presenting for new-onset ED. Clinical, endocrine and metabolic characteristics significantly worsen according to the defined gonadal status.
INTRODUCTION AND OBJECTIVES: Tissue morcellation is an important step during Holmium laser enucle... more INTRODUCTION AND OBJECTIVES: Tissue morcellation is an important step during Holmium laser enucleation of the prostate (HoLEP). This study compares the efficiency of the new VersaCut TM + tissue morcellation system and the older VersaCut TM tissue morcellator system. METHODS: The first 20 patients who underwent HoLEP and tissue morcellation using the new VersaCut TM tissue morcellation system at our institute were included in this study (group1). These patients were matched based on the enucleated tissue weight to patients from our prospectively maintained HoLEP database (group 2) with a 2:1 matching ratio. Peri-operative characteristics, operative times, morcellation times and complications were reported and compared between the two groups. Morcellation efficiency (defined as the weight of morcellated tissue per morcellation time) was calculated and compared between the two groups. RESULTS: The preoperative prostate volume was not different between the two groups [96.9 gm (SD 42) for group 1 vs 97.3 gm (SD 39.8) for group 2, (p¼ 0.967)]. There were no differences in the enucleated weight between the two groups [51.2 gm (SD 26.3) for group 1 vs 50.7gm (SD25.9) for group 2, (p¼0.949)]. Total operative times were not different between the two groups [123.5 minutes (SD 44.1) for group 1 and 152 minutes (SD 55.4) for group 2, p¼ 0.781). When the new morcellator was used, mean morcellation time was 19.9 minuts (SD13.7) whereas mean morcellation time was 14.6 minutes (SD11.6) with the older morcellator (p¼0.122). Morcellation efficiency was comparable between the two groups [3.33 gm/minute (SD1.82) for group 1 vs 4.44 gm/minute (SD 2.45) for group 2]. There were no complications in both groups. When the morcellated tissue was examined postoperatively, there were no differences in the incidence of prostatitis or prostate cancer in the two groups. CONCLUSIONS: When matched by the resected prostatic tissue weight, there were no differences identified in the efficiency of the old VaersaCut TM and the new VersaCut+ TM morcellation systems.
To evaluate the expression of the angiogenic factors vascular endothelial growth factor (VEGF) an... more To evaluate the expression of the angiogenic factors vascular endothelial growth factor (VEGF) and angiopoietins (Ang) 1 and 2, in normal human penile erectile tissue. Penile fragments were removed from four young healthy organ donors (aged 17-28 years), and processed for immunohistochemical studies for VEGF, Ang1 and Ang2, and their specific receptors (VEGFR1 and 2, and Tie2, respectively). Molecular analysis was used to confirm the expression of VEGF and Angs in erectile tissue. VEGF and VEGFR1 expression was restricted to smooth muscle cells (SMCs). VEGFR2 was detected mainly in the endothelium lining and to a lesser extent in the SMC. Ang1 had a scattered distribution mostly in the perivascular SM layer, showing co-localization with VEGF. Tie2 was faintly detected in the endothelial cells. Ang2 was not detected by immunohistochemical studies, but the use of the same antibody in molecular analysis confirmed Ang2 expression in human corpus cavernosum. We show for the first time the co-localization of VEGF and Ang1 in the SMC, suggesting an interaction for vessel stabilization. Ang2 seems to be available for neoangiogenesis, if challenged. Studies of endothelial markers, growth factors and specific receptors are useful for understanding vascular organization and angiogenesis in normal human erectile tissue. This knowledge will be fundamental for developing newer therapeutic approaches to prevent or even cure erectile dysfunction.
Sirtuin (SIRT)1 was recently identified in human corpus cavernosum (CC). We hypothesized that oth... more Sirtuin (SIRT)1 was recently identified in human corpus cavernosum (CC). We hypothesized that other sirtuins could also be expressed in the CC. Expression of these enzymes in tissues is affected by aging, the main independent risk factor for erectile dysfunction besides other cardiovascular disease risk factors (CVDRF), such as diabetes or obesity. The aim of this study was to characterize the expression of SIRT1-3 and SIRT5-7 in human CC relatively to age and CVDRF. Samples of CC collected from patients submitted to programmed surgeries or organ donors were divided in three groups according to age and presence of CVDRF. Expression of SIRT1-3 and SIRT5-7 mRNAs was assessed by real-time polymerase chain reaction. Cellular localization and semi-quantification of sirtuins proteins were performed by immunofluorescence and Western blotting (WB), respectively. Nuclear factor kappa B (NFkB)-p65, inducible (iNOS) and endothelial nitric oxide synthase (eNOS) levels were also assayed by WB. The main outcome measure was to characterize the expression of SIRT1-3 and SIRT5-7 in human CC. SIRT1-3 and SIRT5-7 mRNAs were detected in all individuals, without statistical differences among groups, excepting SIRT7 that decreased four times in aged groups relatively to young (P = 0.013). WB analysis demonstrated that aged individuals with CVDRF presented higher levels of SIRT7 protein relatively to young (P = 0.0495) and lower levels of SIRT3 protein relatively to healthy aged (P = 0.0077). Expression of NFkB-p65 and iNOS were higher in aged than in young individuals (P = 0.0185; P = 0.004, respectively). No differences in other sirtuins or total eNOS were seen among groups although phospho eNOS Ser(1177) levels decreased in groups of aged men relatively to young (P = 0.0043; P = 0.0099). Our results demonstrate for the first time expression of SIRT2-3 and SIRT5-7 in the human CC. Aged individuals with CVDRF presented an increase in SIRT7 protein levels and a decrease in mitochondrial SIRT3. This finding suggests that CVDRF induces the loss of antioxidant defense mechanisms leading to endothelial injury. Freitas M, Rodrigues AR, Tomada N, Fonseca J, Magalhães A, Gouveia AM, Neves D. Effects of aging and cardiovascular disease risk factors on the expression of sirtuins in the human corpus cavernosum. J Sex Med **;**:**-**.
Uploads
Papers by Nuno Tomada