Changes induced by oxidized low-density lipoprotein on prostate stromal cells derived from patients with benign prostatic hyperplasia

Abstract:  Benign Prostatic Hyperplasia (BPH) is a pathology that affects elderly men, being the result of an excessive and uncontrolled cellular proliferative process of both epithelial and stromal prostatic compartments. Novel evidence suggests that dyslipidemias and other factors of the...

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Detalles Bibliográficos
Autores principales: Roldán Gallardo , FF, López Seoane , MR, Maldonado , CA, Quintar , AA
Formato: Artículo revista
Publicado: Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2021
Materias:
Benign prostatic hyperplasia
dyslipidemias
atherosclerosis
hiperplasia prostática
dislipidemias
aterosclerosis
Acceso en línea:https://revistas.unc.edu.ar/index.php/med/article/view/35016
Aporte de:
Revista de la Facultad de Ciencias Médicas de Córdoba de Universidad Nacional de Córdoba
id I10-R327-article-35016
record_format ojs
institution Universidad Nacional de Córdoba
institution_str I-10
repository_str R-327
container_title_str Revista de la Facultad de Ciencias Médicas de Córdoba
format Artículo revista
topic Benign prostatic hyperplasia
dyslipidemias
atherosclerosis
hiperplasia prostática
dislipidemias
aterosclerosis
spellingShingle Benign prostatic hyperplasia
dyslipidemias
atherosclerosis
hiperplasia prostática
dislipidemias
aterosclerosis
Roldán Gallardo , FF
López Seoane , MR
Maldonado , CA
Maldonado , CA
Quintar , AA
Changes induced by oxidized low-density lipoprotein on prostate stromal cells derived from patients with benign prostatic hyperplasia
topic_facet Benign prostatic hyperplasia
dyslipidemias
atherosclerosis
hiperplasia prostática
dislipidemias
aterosclerosis
author Roldán Gallardo , FF
López Seoane , MR
Maldonado , CA
Maldonado , CA
Quintar , AA
author_facet Roldán Gallardo , FF
López Seoane , MR
Maldonado , CA
Maldonado , CA
Quintar , AA
author_sort Roldán Gallardo , FF
title Changes induced by oxidized low-density lipoprotein on prostate stromal cells derived from patients with benign prostatic hyperplasia
title_short Changes induced by oxidized low-density lipoprotein on prostate stromal cells derived from patients with benign prostatic hyperplasia
title_full Changes induced by oxidized low-density lipoprotein on prostate stromal cells derived from patients with benign prostatic hyperplasia
title_fullStr Changes induced by oxidized low-density lipoprotein on prostate stromal cells derived from patients with benign prostatic hyperplasia
title_full_unstemmed Changes induced by oxidized low-density lipoprotein on prostate stromal cells derived from patients with benign prostatic hyperplasia
title_sort changes induced by oxidized low-density lipoprotein on prostate stromal cells derived from patients with benign prostatic hyperplasia
description Abstract:  Benign Prostatic Hyperplasia (BPH) is a pathology that affects elderly men, being the result of an excessive and uncontrolled cellular proliferative process of both epithelial and stromal prostatic compartments. Novel evidence suggests that dyslipidemias and other factors of the Metabolic Syndrome are associated to BPH progression and aggressiveness. However, little information is available about the pathogenic mechanisms promoting prostatic growth in atherogenic contexts. We, therefore, aimed to analyze in vitro the effects of oxidized low-density lipoprotein (OxLDL) on primary cell cultures. Prostatic stromal cells, surgically harvested from patients with BPH (n=3), were isolated, cultured, and stimulated with OxLDL (20 μM or 100 μM, simulating an atherogenic state) or vehicle for 24 h and 48 h. In this context, OxLDL induced cell proliferation, as assessed by BrdU incorporation and Ki67 immunocytochemistry, mainly at lower concentrations and in a time-dependent manner (p<0.001 vs. vehicle). OxLDL-treated cells also displayed a myofibroblastic phenotype with high metabolic activity, characterized by an increase of cytoplasmic granules, dilated endoplasmic reticulum, and the presence of prominent nucleoli, as evaluated by transmission electron microscopy (TEM). Furthermore, the release and characterization of Extracellular Vesicles (EVs) were determined in supernatants, which were isolated by ultracentrifugation steps and observed by TEM using negative staining. BPH-derived stromal cells showed a very low frequency of secreted EVs, with OxLDL inducing a 10-fold increase, especially in a fraction of 15-20 nm (p<0.001). At ultrastructural level, these vesicles exhibited an artificial concave shape appearance, compatible with exosomes. Taken together, these findings indicate that OxLDL promotes cell proliferation, stimulation, and EVs release in BPH stromal cells, pointing OxLDL as a strong pathogenic factor in atherogenic contexts supporting uncontrolled prostatic growth.
publisher Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
publishDate 2021
url https://revistas.unc.edu.ar/index.php/med/article/view/35016
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spelling I10-R327-article-350162024-04-15T16:19:09Z Changes induced by oxidized low-density lipoprotein on prostate stromal cells derived from patients with benign prostatic hyperplasia Cambios inducidos por la lipoproteína de baja densidad oxidada sobre células estromales prostáticas derivadas de pacientes con hiperplasia prostática benigna Roldán Gallardo , FF López Seoane , MR Maldonado , CA Maldonado , CA Quintar , AA Benign prostatic hyperplasia dyslipidemias atherosclerosis hiperplasia prostática dislipidemias aterosclerosis Abstract:  Benign Prostatic Hyperplasia (BPH) is a pathology that affects elderly men, being the result of an excessive and uncontrolled cellular proliferative process of both epithelial and stromal prostatic compartments. Novel evidence suggests that dyslipidemias and other factors of the Metabolic Syndrome are associated to BPH progression and aggressiveness. However, little information is available about the pathogenic mechanisms promoting prostatic growth in atherogenic contexts. We, therefore, aimed to analyze in vitro the effects of oxidized low-density lipoprotein (OxLDL) on primary cell cultures. Prostatic stromal cells, surgically harvested from patients with BPH (n=3), were isolated, cultured, and stimulated with OxLDL (20 μM or 100 μM, simulating an atherogenic state) or vehicle for 24 h and 48 h. In this context, OxLDL induced cell proliferation, as assessed by BrdU incorporation and Ki67 immunocytochemistry, mainly at lower concentrations and in a time-dependent manner (p<0.001 vs. vehicle). OxLDL-treated cells also displayed a myofibroblastic phenotype with high metabolic activity, characterized by an increase of cytoplasmic granules, dilated endoplasmic reticulum, and the presence of prominent nucleoli, as evaluated by transmission electron microscopy (TEM). Furthermore, the release and characterization of Extracellular Vesicles (EVs) were determined in supernatants, which were isolated by ultracentrifugation steps and observed by TEM using negative staining. BPH-derived stromal cells showed a very low frequency of secreted EVs, with OxLDL inducing a 10-fold increase, especially in a fraction of 15-20 nm (p<0.001). At ultrastructural level, these vesicles exhibited an artificial concave shape appearance, compatible with exosomes. Taken together, these findings indicate that OxLDL promotes cell proliferation, stimulation, and EVs release in BPH stromal cells, pointing OxLDL as a strong pathogenic factor in atherogenic contexts supporting uncontrolled prostatic growth. Resumen:  La hiperplasia prostática benigna (HPB) es una patología que afecta a hombres de edad avanzada, siendo el resultado de un proceso proliferativo celular excesivo y descontrolado de los compartimentos prostáticos, tanto epitelial como estromal. Nuevas evidencias sugieren que las dislipidemias y otros factores del síndrome metabólico se encuentran asociados con la progresión y la agresividad de la HPB. No obstante, existe poca información disponible sobre los mecanismos patogénicos que promueven el crecimiento prostático en contextos aterogénicos. Por lo tanto, nuestro objetivo fue analizar in vitro los efectos de la lipoproteína de baja densidad oxidada (OxLDL) en cultivos celulares primarios. Las células estromales prostáticas, extraídas quirúrgicamente de pacientes con HPB (n = 3) se aislaron, cultivaron y estimularon con OxLDL (20 µM o 100 µM, simulando un estado aterogénico) o vehículo durante 24 y 48 horas. En este contexto, OxLDL produjo un aumento en la tasa de proliferación celular; según lo evaluado mediante la incorporación de BrdU e inmunocitoquímica de Ki67, principalmente a concentraciones bajas y dependiente del tiempo (p<0,001 frente al vehículo). A su vez, las células tratadas con OxLDL mostraron un fenotipo miofibroblástico con alta actividad metabólica, caracterizado por un aumento de gránulos citoplasmáticos, retículo endoplásmico dilatado y la presencia de nucléolos prominentes; observados y evaluados por microscopía electrónica de transmisión (TEM). Asimismo, se determinó la liberación y caracterización de vesículas extracelulares (EVs) a partir de sobrenadantes, las cuales fueron aisladas mediante ultracentrifugación, contrastadas con tinción negativa y analizadas por TEM. Las células estromales prostáticas mostraron una frecuencia muy baja de EVs secretadas, con OxLDL induciendo un aumento de hasta 10 veces, especialmente en el rango de EVs de 15-20 nm (p <0,001). A nivel ultraestructural, estas vesículas exhibían una apariencia de forma cóncava artificial, compatible con la de exosomas. En conjunto, estos hallazgos indican que OxLDL promueve la proliferación celular, la estimulación y la liberación de EVs en las células estromales prostáticas derivadas de pacientes con HPB, lo que señala a OxLDL como un fuerte factor patogénico en contextos aterogénicos, promoviendo el crecimiento prostático descontrolado. Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2021-10-12 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion texto texto texto https://revistas.unc.edu.ar/index.php/med/article/view/35016 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 78 No. Suplemento (2021): Suplemento JIC XXII Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 78 Núm. Suplemento (2021): Suplemento JIC XXII Revista da Faculdade de Ciências Médicas de Córdoba; v. 78 n. Suplemento (2021): Suplemento JIC XXII 1853-0605 0014-6722 http://creativecommons.org/licenses/by-nc/4.0

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