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二氢睾酮通过雄激素受体依赖性机制增强人内皮祖细胞的血管生成和迁移潜能。

Dihydrotestosterone Augments the Angiogenic and Migratory Potential of Human Endothelial Progenitor Cells by an Androgen Receptor-Dependent Mechanism.

机构信息

Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 050568 Bucharest, Romania.

Department for Reproductive Endocrinology, University Zurich, 8006 Zürich, Switzerland.

出版信息

Int J Mol Sci. 2024 Apr 29;25(9):4862. doi: 10.3390/ijms25094862.

DOI:10.3390/ijms25094862
PMID:38732080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11084206/
Abstract

Endothelial progenitor cells (EPCs) play a critical role in cardiovascular regeneration. Enhancement of their native properties would be highly beneficial to ensuring the proper functioning of the cardiovascular system. As androgens have a positive effect on the cardiovascular system, we hypothesized that dihydrotestosterone (DHT) could also influence EPC-mediated repair processes. To evaluate this hypothesis, we investigated the effects of DHT on cultured human EPCs' proliferation, viability, morphology, migration, angiogenesis, gene and protein expression, and ability to integrate into cardiac tissue. The results showed that DHT at different concentrations had no cytotoxic effect on EPCs, significantly enhanced the cell proliferation and viability and induces fast, androgen-receptor-dependent formation of capillary-like structures. DHT treatment of EPCs regulated gene expression of androgen receptors and the genes and proteins involved in cell migration and angiogenesis. Importantly, DHT stimulation promoted EPC migration and the cells' ability to adhere and integrate into murine cardiac slices, suggesting it has a role in promoting tissue regeneration. Mass spectrometry analysis further highlighted the impact of DHT on EPCs' functioning. In conclusion, DHT increases the proliferation, migration, and androgen-receptor-dependent angiogenesis of EPCs; enhances the cells' secretion of key factors involved in angiogenesis; and significantly potentiates cellular integration into heart tissue. The data offer support for potential therapeutic applications of DHT in cardiovascular regeneration and repair processes.

摘要

内皮祖细胞（EPCs）在心血管再生中起着关键作用。增强其固有特性将非常有利于确保心血管系统的正常功能。由于雄激素对心血管系统有积极影响，我们假设二氢睾酮（DHT）也可能影响 EPC 介导的修复过程。为了评估这一假设，我们研究了 DHT 对培养的人 EPC 增殖、活力、形态、迁移、血管生成、基因和蛋白表达以及整合到心脏组织中的能力的影响。结果表明，不同浓度的 DHT 对 EPC 无细胞毒性作用，显著增强了细胞增殖和活力，并诱导快速、雄激素受体依赖性形成毛细血管样结构。DHT 处理 EPCs 调节了雄激素受体的基因表达以及参与细胞迁移和血管生成的基因和蛋白。重要的是，DHT 刺激促进了 EPC 的迁移以及细胞黏附和整合到鼠心脏切片中的能力，表明其在促进组织再生方面发挥作用。质谱分析进一步强调了 DHT 对 EPC 功能的影响。总之，DHT 增加了 EPC 的增殖、迁移和雄激素受体依赖性血管生成；增强了细胞分泌参与血管生成的关键因子；并显著增强了细胞整合到心脏组织中的能力。这些数据为 DHT 在心血管再生和修复过程中的潜在治疗应用提供了支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e5e/11084206/6a31f102da3d/ijms-25-04862-g010.jpg
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