Abstract: Erectile dysfunction (ED) is a highly prevalent disease whose aetiology is mostly vasculogenic. It is nowadays considered a marker of future cardiovascular events reflecting the underlying endothelial dysfunction, the common link with the metabolic syndrome (MetS). The recent association between MetS, endothelial dysfunction and peripheral artery disease, but not with coronary artery disease (CAD), suggests that the pathophysiologies of CAD and peripheral artery disease may be distinct. Moreover, several recent studies support an emerging role for an imbalance of angiogenic growth factor levels like Angiopoietin 1 and 2 in cardiovascular disease, considering its intimate association with chronic low-grade inflammation. We aim to find a correlation between Angiopoietins levels and systemic and local endothelial function in MetS and ED patients. Forty-five MetS patients with ED were enrolled. ED severity was assessed by International Index of Erectile Function questionnaire (IIEF5) and penile duplex Doppler ultrasound (PDDU). Endothelial function was assessed by Peripheral arterial tonometry (PAT), and serum asymmetric dimethylarginine (ADMA), Ang1 and Ang2 levels. Obesity and hypertension were the most frequent MetS parameters (91.1 and 88.9% respectively). Severe ED was present in 35.6% of patients. Penile haemodynamic was impaired in 77.5%. Endothelial dysfunction (PAT criteria) was present in 40.9% of patients. Ang2 levels were significantly higher in men with abdominal obesity. We observed an inverse correlation between Ang1 and peak systolic velocity, and in patients with penile arterial dysfunction, Ang1 levels were significantly higher and Ang2/Ang1 ratio significantly lower, than patients with normal arterial function. Neither ADMA nor PAT parameters were correlated with ED severity evaluated by IIEF5 or PDDU exam. In conclusion, there is an imbalance of angiopoietins in MetS and ED patients. The absence of correlation with PAT or ADMA levels suggests that angiopoietins may be early markers of endothelial dysfunction in this population of higher cardiovascular risk.
Abstract: Peyronie's disease is an acquired penile deformity with a variety of presentations, caused by the formation of fibrous plaques within the tunica albuginea, leading to bio-mechanical and vascular abnormalities. The objective is to investigate the 18 years outcome of patients with Peyronie's disease treated with penile corporoplasty (Yachia technique) in our department.
Abstract: Abstract Aims: Analyze the capacity of ICO, the ratio of waist circumference (WC) and height, in predicting hemodynamic impairment in Erectile Dysfunction (ED) patients, independently and integrated in Metabolic Syndrome (MetS) definitions. Methods: Four hundred and eighty-five ED patients followed in Urology consult from January 2008 until March 2012 were evaluated by a standardized protocol: health questionnaire, anthropometric measurements (AM), blood pressure and analysis, and Penile Duplex Doppler Ultrasound (PDDU) exam. Associations between AM and MetS definitions, including ATPIII, IDF and a new definition replacing WC by ICO in ATPIII MetS definition (ModATPIII), and PDDU were calculated. Results: ICO was the measure of obesity more strongly correlated with diminished mean Peak Systolic Velocity (mPSV) (r = -0.189, p < 0.001). A positive association remained when replacing WC by ICO ≥ 0.60 (a nationally obtained ratio) in ATPIII MetS definition (ModATPIII). Patients with ModATPIII had lower mPSV when compared to non-MetS patients (30.8 versus 37.1, p < 0.001). Only the IDF definition had a significant association with AD (OR = 1853; 95%CI, 1.202-2.857). Conclusions: ICO revealed potential value to predict PDDU changes in a MetS context. However, IDF definition presented a stronger correlation with arteriogenic ED. Although longitudinal studies are necessary to confirm this hypothesis, our study highlights the importance of different MetS definitions for ED assessment.
Abstract: Forecast of success with testicular sperm extraction and intracytoplasmic sperm injection (ICSI) remains unknown, as predictive factors have rarely been studied. We evaluated the association among possible predictive factors and a successful biopsy and clinical pregnancy. A consecutive sample of men submitted to a testicular open biopsy in S. João Hospital was used. Patient's age, medical history, testicular volume, spermogram, genetic testing, endocrinologic results, biopsy results and clinical pregnancy information were collected. From the 113 men included, it was possible to retrieve spermatozoa in 79.6% of the cases, which resulted in 58 fertilisations and 22 clinical pregnancies. Retrieving viable spermatozoa on biopsy was associated with the identification of spermatozoa in the spermogram (100.0% versus 74.4%; P = 0.010), diseases causing obstructive infertility (100.0% versus 79.2%; P = 0.036) and no genetic causes detected (82.4% versus 54.5%; P = 0.030). Successful clinical pregnancy was only associated with lower female partner age (31.7 versus 36.0 year; P = 0.001) but not the quality of the spermatozoa or the time until the reproduction cycle. Identification of spermatozoa in the spermogram, diseases causing obstructive infertility and lack of genetic causes for infertility were associated with higher probability of viable spermatozoa retrieval but the female partner age remained the principal determinant of a successful pregnancy.
Abstract: The purpose of the current study was to evaluate the effect of a high-fat (HF) diet, energy restriction and exercise on the expression of vascular endothelial growth factor (VEGF), angiopoietin (Ang) 1 and 2, and their receptors in rat corpus cavernosum (CC). Male Wistar rats were fed ad libitum with an HF diet for 8 or 16 weeks. After 8 weeks of the HF diet, a group of rats was subjected to energy restriction with or without exercise for 8 weeks. Control animals had free access to standard diet for the same period. After euthanasia, blood was collected and the penises removed for immunofluorescence assays (VEGF, VEGF receptor (VEGFR) 1 and 2, Ang1, Ang2 and Tie2) and semiquantification of VEGF, VEGFR1, VEGFR2, Ang1, Ang2, Tie2, endothelial nitric oxide synthase (eNOS) and Akt/phospho-Akt by Western blotting. HF diet-fed rats exhibited lower high-density lipoprotein cholesterol (HDL-c) levels, higher systolic blood pressure and an increased atherogenic index. A significant increase in Ang2 expression in the CC was verified and coupled to a decrease in VEGF and VEGFRs. The Akt pathway was activated by the HF diet. Energy restriction and exercise increased eNOS expression and restored most HF diet-induced modifications except for VEGFR2 expression. These results emphasize the role of diet on vascular function regulation, demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/Tie2 systems occurs before serum lipid changes and obesity onset, antedating structural atherosclerotic features.
Abstract: Aging and physiological androgen decay leads to structural changes in corpus cavernosum (CC) that associate with erectile function impairment. There is evidence that such changes relate to nitric oxide (NO) bioavailability, an endothelial compound produced by the action of endothelial NO synthase (eNOS), and is regulated by sirtuin-1 (Sirt1), a NAD(+)-dependent protein deacetylase. Taking into account the reduced NO synthesis observed in aging and erectile dysfunction, we aimed to characterize human CC of androgen-deprived, young, and aged individuals postulating that androgen deprivation induces modifications similar to those observed in aging. Human penile fragments were collected from young individuals submitted to male-to-female sex reassignment procedure, who undergone an androgen deprivation chemical regimen, from young organ donors and from aged patients submitted to penile deviation surgery. They were processed for histomorphometric analysis of smooth muscle (SM) and connective tissues (CT), and dual-immunofluorescence of alpha-actin/vWf or Sirt1, and endothelin-1/eNOS. Estrogen receptors were analyzed by immunohistochemistry and semiquantification of Sirt1, eNOS, and phospho-Akt was assayed by Western blotting. Androgen withdrawal, similarly to aging, leads to a noteworthy reduction of SM-to-CT ratio in CC. However, in contrast to young and aged, a significant increase in penile Sirt1 expression accompanied by an increase in total eNOS expression was observed in androgen-depleted individuals. No changes were evidenced in phospho-Akt system and estrogen receptors were undetectable. These findings indicate that Sirt1 regulates the expression of eNOS in human CC employing mechanisms influenced by androgen depletion.
Abstract: Aging is a recognized risk factor for erectile dysfunction (ED), contributing independently to vascular damage of penile tissue. Vascular maintenance depends on angiogenic balance in tissues. Vascular endothelial growth factor (VEGF) is a modulator of endothelial cells functions, after engagement to specific receptor kinase domain region (KDR). Other factors, such as angiopoietins, cross talk with VEGF, modulating its effects. Angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) compete for binding to Tie-2 and, while Ang1 promotes vascular stabilization, Ang2 acts as a partial agonist or antagonist of Ang1 signaling, depending on VEGF bioavailability.
Abstract: Erectile dysfunction (ED) is a common disease that is mostly vasculogenic in nature. ED correlates with cardiovascular risk factors, with endothelial dysfunction being the common link. Hypertension (HTA) and insulin resistance are the most important determinants of arteriogenic ED, and are also components of the metabolic syndrome (MetS), which supports a strong association between MetS and ED. However, MetS and, specifically, obesity interference on penile hemodynamics is still controversial.
Abstract: 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.
Abstract: Erectile dysfunction (ED) is a highly prevalent and age-related disease, caused by endothelial dysfunction and impaired cavernous angiogenesis. However, cellular and molecular changes involved in erectile pathophysiology in aging male remain to be elucidated.
Abstract: Erectile Dysfunction (ED), the inability to achieve or maintain an erection of sufficient rigidity for completion of sexual act, is a common condition affecting more than 150 million of men worldwide. This disorder is highly associated with aging, however concomitant pathologies such as hyperlipidemia, hypertension, and diabetes also contribute to ED progression. In the Massachusetts Male Aging Study, age was considered an independent variable strongly associated with ED, showing that the prevalence of this disease increased with age from 38% in the youngest group of men (mean age 40 y.) to almost 70% in the oldest group of men examined (mean age 70 y.). It is well demonstrated that aging leads to changes in the cardiovascular system, which results in a decrease in elasticity due to fibrosis and an increase in stiffness of the arterial system, independently of the effects of concurrent pathologies. Vasculogenic ED is the most prevalent condition, affecting nearly 80% of patients with organic etiology. Small vessels of the penis are very sensitive to structural and functional changes, and small disturbances can conduce to ED. ED is now considered by some authors as synonymous to endothelial dysfunction and an early manifestation of atherosclerosis, being a precursor of systemic vascular disease. Human cavernous tissue is mainly constituted by smooth muscle fibers that surround sinusoid vessels. Corpus cavernosum structural elements act in concert, allowing increase of intra-cavernous arterial flow and smooth muscle relaxation processes which are fundamental to penile erection. The aim of this study was to compare the ultrastructural anatomy of the young and aged human corpus cavernosum, in the absence of additional risk factors.
Abstract: The main cause of erectile dysfunction (ED) is organic in nature, with vasculogenic etiology being predominant. Several epidemiological studies report the relationship between ED and several well-recognized cardiovascular risk factors, including atherosclerosis, diabetes, dyslipidemia, hypertension, as well as lifestyle factors, such as obesity and sedentarism. Recent findings also indicate that high-fat (HF) regular intake induces endothelial dysfunction and increases ED prevalence. Due to their interconnection, ED is considered equivalent to endothelial dysfunction, and it is nowadays seen as a predictive factor of atherosclerosis and cardiovascular disease (CVD). It is well established that the expression of some vascular growth factors is frequently diminished in corpus cavernosum (CC) of ED patients, and that its levels are particularly modified in metabolic syndrome (MetS). This syndrome combines more than three of the illnesses that prompt to vasculogenic ED: elevated blood pressure, high triglycerides, low high-density lipoprotein (HDL) cholesterol, elevated waist circumference, and insulin resistance. Hepatocyte Growth Factor (HGF) is a pleiotropic factor with potent mitogenic and angiogenic properties, previously employed in the treatment of ischaemic members. Interestingly, it was demonstrated that its serum levels were particularly increased in obesity and in MetS. HGF is expressed by several organs, but as far as we know, it has never been detected in CC. In this way, we present an immunohistochemical (IH) characterization of HGF expression in HF-diet fed rat CC.
Abstract: 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.
