Weber Callie M, Harris Mikayla N, Zic Sophia M, Sangha Gurneet S, Arnold Nicole S, Dluzen Douglas F, Clyne Alisa Morss
Fischell Department of Bioengineering, University of Maryland, 8278 Paint Branch Dr., College Park, MD 20742 USA.
Department of Biology, Morgan State University, Baltimore, MD 21251 USA.
Cell Mol Bioeng. 2023 Apr 12;16(2):127-141. doi: 10.1007/s12195-023-00762-2. eCollection 2023 Apr.
Women are at elevated risk for certain cardiovascular diseases, including pulmonary arterial hypertension, Alzheimer's disease, and vascular complications of diabetes. Angiotensin II (AngII), a circulating stress hormone, is elevated in cardiovascular disease; however, our knowledge of sex differences in the vascular effects of AngII are limited. We therefore analyzed sex differences in human endothelial cell response to AngII treatment.
Male and female endothelial cells were treated with AngII for 24 h and analyzed by RNA sequencing. We then used endothelial and mesenchymal markers, inflammation assays, and oxidative stress indicators to measure female and male endothelial cell functional changes in response to AngII.
Our data show that female and male endothelial cells are transcriptomically distinct. Female endothelial cells treated with AngII had widespread gene expression changes related to inflammatory and oxidative stress pathways, while male endothelial cells had few gene expression changes. While both female and male endothelial cells maintained their endothelial phenotype with AngII treatment, female endothelial cells showed increased release of the inflammatory cytokine interleukin-6 and increased white blood cell adhesion following AngII treatment concurrent with a second inflammatory cytokine. Additionally, female endothelial cells had elevated reactive oxygen species production compared to male endothelial cells after AngII treatment, which may be partially due to nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX2) escape from X-chromosome inactivation.
These data suggest that endothelial cells have sexually dimorphic responses to AngII, which could contribute to increased prevalence of some cardiovascular diseases in women.
The online version contains supplementary material available at 10.1007/s12195-023-00762-2.
女性患某些心血管疾病的风险较高，包括肺动脉高压、阿尔茨海默病和糖尿病的血管并发症。血管紧张素II（AngII）是一种循环应激激素，在心血管疾病中水平升高；然而，我们对AngII血管作用中的性别差异了解有限。因此，我们分析了人类内皮细胞对AngII治疗反应中的性别差异。
用AngII处理男性和女性内皮细胞24小时，并通过RNA测序进行分析。然后，我们使用内皮细胞和间充质标志物、炎症检测和氧化应激指标来测量男性和女性内皮细胞对AngII反应的功能变化。
我们的数据表明，男性和女性内皮细胞在转录组上存在差异。用AngII处理的女性内皮细胞有与炎症和氧化应激途径相关的广泛基因表达变化，而男性内皮细胞的基因表达变化很少。虽然男性和女性内皮细胞在AngII处理后都保持其内皮细胞表型，但女性内皮细胞在AngII处理并与第二种炎症细胞因子同时存在时，显示出炎症细胞因子白细胞介素-6的释放增加和白细胞粘附增加。此外，与AngII处理后的男性内皮细胞相比，女性内皮细胞的活性氧生成增加，这可能部分归因于烟酰胺腺嘌呤二核苷酸磷酸氧化酶-2（NOX2）逃避X染色体失活。
这些数据表明内皮细胞对AngII有性别二态性反应，这可能导致女性某些心血管疾病的患病率增加。
在线版本包含可在10.1007/s12195-023-00762-2获取的补充材料。
