Institute of Comparative Molecular Endocrinology (CME), Ulm University, Germany (U.S., G.C., J.T.).
Department of Medicine IV, University Hospital, LMU Munich, Germany (F.V., M.R.).
Hypertension. 2023 Nov;80(11):2333-2344. doi: 10.1161/HYPERTENSIONAHA.123.21185. Epub 2023 Aug 30.
Cushing syndrome (CS) is a rare disease caused by excess cortisol levels with high cardiovascular morbidity and mortality. Hypertension in CS promotes hypercortisolism-associated cardiovascular events. Adipose tissue is a highly plastic tissue with most cell types strongly affected by the excess cortisol exposure. We hypothesized that the molecular and cellular changes of periadrenal adipose tissue in response to cortisol excess impact systemic blood pressure levels in patients with CS.
We investigated gene expression signatures in periadrenal adipose tissue from patients with adrenal CS collected during adrenal surgery.
During active CS we observed a downregulation of gene programs associated with inflammation in periadrenal adipose tissue. In addition, we observed a clustering of the patients based on tissue gene expression profiles into 2 groups that differed in blood pressure levels (CS low blood pressure and CS high blood pressure). The 2 clusters showed significant differences in gene expression pattens of the renin-angiotensin-aldosterone-system. Renin was the strongest regulated gene compared with control patients and its expression correlated with increased blood pressure observed in our patients with CS. In the CS high blood pressure group, systemic renin plasma levels were suppressed indicative of an abnormal blood pressure associated with periadrenal adipose tissue renin-angiotensin-aldosterone-system activation.
Here, we show for the first time a relevant association of the local renin-angiotensin-aldosterone-system and systemic blood pressure levels in patients with CS. Patients from the CS high blood pressure group still had increased blood pressure levels after 6 months in remission, highlighting the importance of local tissue effects on long-term systemic effects observed in CS.
库欣综合征（CS）是一种由皮质醇水平过高引起的罕见疾病，具有较高的心血管发病率和死亡率。CS 中的高血压会促进与皮质醇过高相关的心血管事件。脂肪组织是一种高度可塑的组织，大多数细胞类型都受到皮质醇暴露的强烈影响。我们假设，肾上腺周围脂肪组织对皮质醇过多的分子和细胞变化会影响 CS 患者的全身血压水平。
我们研究了在肾上腺手术期间收集的肾上腺 CS 患者的肾上腺周围脂肪组织中的基因表达谱。
在活跃的 CS 中，我们观察到肾上腺周围脂肪组织中与炎症相关的基因程序下调。此外，我们观察到患者根据组织基因表达谱聚类为 2 组，这 2 组在血压水平上存在差异（CS 低血压和 CS 高血压）。这 2 个聚类在肾素-血管紧张素-醛固酮系统的基因表达模式上存在显著差异。与对照患者相比，肾素是调节最强的基因，其表达与我们 CS 患者观察到的血压升高相关。在 CS 高血压组中，全身肾素血浆水平受到抑制，表明与肾上腺周围脂肪组织肾素-血管紧张素-醛固酮系统激活相关的异常血压。
在这里，我们首次显示 CS 患者局部肾素-血管紧张素-醛固酮系统与全身血压水平之间存在相关关系。CS 高血压组患者在缓解后 6 个月仍有较高的血压水平，这突出了局部组织对 CS 中观察到的长期全身效应的重要性。
