Calcification of the cavernosal bodies may be responsible for development of erectile dysfunction in uremic apolipoprotein E deficient (apoE-/-) mice / Calcificación de cuerpos cavernosos y desarrollo de disfunción eréctil en la falta de apolipoproteína urémica E (ratones ApoE-/-) en un modelo de ratón

INTRODUCTION AND OBJECTIVE: Erectile dysfunction's physiopathology in uremia is complex and multifactorial, involving a combination of classical risk factors and specific uremia-related risk factors such as increased oxidative stress, endothelial dysfunction and inflammation. The aim of the study is to investigate the effect of chronic kidney disease (CKD) on vascular calcification and endothelial function of cavernosal bodies in apolipoprotein E deficient (apoE−/−) mice, a well known model of erectile dysfunction. MATERIALS AND METHODS: Eight-week-old male apoE−/− mice were randomly assigned to the following 3 groups: (I) subtotally nephrectomised (SNX apoE−/−, 12 mice), (II) uninephrectomised (UNX apoE−/−, 11 mice) or (III) sham operated (sham-op apoE−/−, 15 mice). At 16 weeks after surgery, aortas and penile erectile tissues were harvested for histological studies to assess atherosclerosis, vascular calcification, nitrotyrosine staining, total collagen content and macrophage staining. RESULTS: At sacrifice, SNX and UNX mice had significantly higher serum urea, total cholesterol, and triglyceride concentrations than sham-op controls. Atherosclerotic lesions in thoracic aorta were significantly larger in uremic apoE−/− mice than in controls. There were no atheromatous lesions in cavernosal bodies or penile artery observed in any group. However, SNX and UNX animals showed a significant increase in calcification score, collagen content and nitrotyrosine staining in cavernosal bodies when compared with controls. The degree of macrophage infiltration was comparable between the 3 groups. CONCLUSION: In conclusion, even mild renal dysfunction, i.e., after uninephrectomy increases calcification score and aggravates endothelial function of cavernosal bodies in apoE−/− mice and this effect might be linked to increased oxidative stress in penile endothelium

INTRODUCCIÓN Y OBJETIVOS: La fisiopatología de la disfunción eréctil en la uremia es compleja y multifactorial, e incluye una combinación de factores de riesgo clásicos y factores específicos asociados a la uremia, como el aumento del estrés oxidativo, la disfunción endotelial y la inflamación. El objetivo de este trabajo es examinar el efecto de la enfermedad renal crónica (ERC) sobre la calcificación vascular y la función endotelial de los cuerpos cavernosos en caso de deficiencia de apolipoproteína E en ratones (ratones ApoE−/−), un modelo bien conocido de disfunción eréctil. MATERIALES Y MÉTODOS: Los ratones machos de 8 semanas de edad con «ApoE−/−mice» se distribuyen aleatoriamente en 3 grupos: 1) con heminefrectomía (SNX ApoE−/−), 12 ratones; 2) con nefrectomía única (UNX ApoE−/−), 11 ratones, y 3) operación de placebo (sham-op ApoE−/−), 15 ratones. Dieciséis semanas después de la cirugía, se retiraron los tejidos eréctiles de la aorta y el pene para realizar estudios histológicos con el fin de evaluar la aterosclerosis, la calcificación vascular, las sombras de nitrotirosina, el contenido de colágeno total y las sombras de macrófagos. RESULTADOS: Durante el sacrificio, los ratones con SNX y UNX reflejaron valores de urea sérica, colesterol total y concentración de triglicéridos significativamente más elevados, en comparación con los casos controlados con placebo. Las lesiones ateroscleróticas en la aorta torácica fueron mucho mayores en los ratones urémicos «ApoE−/−» en comparación con los controles. No hubo lesiones ateromatosas en los cuerpos cavernosos ni en la arteria del pene en ninguno de los grupos. Sin embargo, los animales con nefrectomía seminal y única mostraron un aumento significativo en la calcificación, presencia de colágeno y manchas de nitrotirosina en cuerpos cavernosos en comparación con los controles. El grado de infiltración de macrófagos fue comparable entre los 3 grupos. CONCLUSIÓN: Se ha concluido que incluso una disfunción renal menor, es decir, tras una nefrectomía única, aumenta la calcificación y exacerba la función endotelial de los cuerpos cavernosos en ratones «ApoE−/−», y este efecto puede estar asociado a un aumento del estrés oxidativo en el endotelio del pene

Calcification of the cavernosal bodies may be responsible for development of erectile dysfunction in uremic apolipoprotein E deficient (apoE-/-) mice.

INTRODUCTION AND OBJECTIVE: Erectile dysfunction's physiopathology in uremia is complex and multifactorial, involving a combination of classical risk factors and specific uremia-related risk factors such as increased oxidative stress, endothelial dysfunction and inflammation. The aim of the study is to investigate the effect of chronic kidney disease (CKD) on vascular calcification and endothelial function of cavernosal bodies in apolipoprotein E deficient (apoE-/-) mice, a well known model of erectile dysfunction. MATERIALS AND METHODS: Eight-week-old male apoE-/- mice were randomly assigned to the following 3 groups: (i) subtotally nephrectomised (SNX apoE-/-, 12 mice), (ii) uninephrectomised (UNX apoE-/-, 11 mice) or (iii) sham operated (sham-op apoE-/-, 15 mice). At 16 weeks after surgery, aortas and penile erectile tissues were harvested for histological studies to assess atherosclerosis, vascular calcification, nitrotyrosine staining, total collagen content and macrophage staining. RESULTS: At sacrifice, SNX and UNX mice had significantly higher serum urea, total cholesterol, and triglyceride concentrations than sham-op controls. Atherosclerotic lesions in thoracic aorta were significantly larger in uremic apoE-/- mice than in controls. There were no atheromatous lesions in cavernosal bodies or penile artery observed in any group. However, SNX and UNX animals showed a significant increase in calcification score, collagen content and nitrotyrosine staining in cavernosal bodies when compared with controls. The degree of macrophage infiltration was comparable between the 3 groups. CONCLUSION: In conclusion, even mild renal dysfunction, i.e., after uninephrectomy increases calcification score and aggravates endothelial function of cavernosal bodies in apoE-/- mice and this effect might be linked to increased oxidative stress in penile endothelium.

Compared With Radical Nephrectomy, Nephron-sparing Partial Nephrectomy Protects Apolipoprotein E-deficient Mice From Atherosclerosis Progression.

OBJECTIVE: To compare the effect of radical with partial unilateral nephrectomy on the development of atherosclerosis in the apolipoprotein E (apoE(-/-))-deficient mouse model. METHODS: Male apoE(-/-) mice were randomly assigned to the following 3 groups: (1) radical left nephrectomy (RNX, 15 mice), (2) partial left nephrectomy (PNX, 15 mice), and (3) left kidney sham operation (sham-op, 12 mice). The right kidney was left intact in all groups. At 16 weeks after surgery, mice were killed, and atherosclerotic surface area and plaque composition were evaluated in the aortic root and the descending aorta using a quantitative morphologic image processing method. RESULTS: At killing, RNX mice had significantly higher serum urea, total cholesterol, and triglyceride concentrations than PNX and sham-op groups (P <.05, P <.001, and P <.0001, respectively). Atherosclerotic lesions in the aortic root and the descending aorta were significantly increased in the RNX mice compared with those in the PNX and sham-op mice (P <.05 and P <.001, respectively). In addition, aortic plaques of RNX mice showed a significant increase in nitrotyrosine expression (P <.02) and collagen content (P <.05), whereas the degree of macrophage infiltration was comparable between the groups. CONCLUSION: We show for the first time that PNX, as compared with RNX, slows the progression of vascular disease in a mouse model of severe atherosclerosis. This effect was mediated by the prevention of chronic kidney disease-induced increases in oxidative stress and lipid disturbances. Our finding can be interpreted as being in support of an expanded use of nephron-sparing techniques in atherosclerosis-prone patients who need to undergo kidney cancer surgery.