Oestrogen and oestrogen metabolites in pulmonary arterial hypertension

肺动脉高压中的雌激素和雌激素代谢物

• 批准号: MR/T015713/1
• 负责人: Margaret MacLean
• 金额: $ 89.66万
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT015713%2F1
• 关键词: Oestrogen; oestrogen; metabolites; pulmonary; arterial

Pulmonary Arterial Hypertension (PAH) is a disease where the blood vessels of the lungs thicken and close down. This puts strain on the right side of the heart which eventually fails. Survival is very poor and many more women than men get this disease. The sex hormone oestrogen (E2) can cause similar changes to the blood vessels and this may be due to them being broken down (metabolised) in the body to other more toxic chemicals. Many clinical trials are ongoing using drugs that interfere with the effects of E2. Using a novel assay we will measure E2 and its metabolites in the blood taken from patients with PAH and see how the change with disease severity, sex, age and obesity. We will also examine how the lungs themselves metabolise E2 in patients. We will analyse blood from patients in clinical trials for drugs that affect E2. We will to see how the drugs affect E2 and its metabolism and how this relates to the therapeutic effects of the drugs. We will examine lung blood vessel cells from patients with PAH and examine how E2 and its metabolites affect the way they grow and move. We will also study a rat model of PAH to determine how E2 metabolism changes during the development of the disease and is affected by the sex of the animal.

肺动脉高压（PAH）是一种肺血管扩张和关闭的疾病。这给心脏的右侧带来了压力，最终导致心脏衰竭。存活率很低，患这种疾病的妇女比男子多得多。性激素雌激素（E2）也会对血管造成类似的变化，这可能是由于它们在体内被分解（代谢）为其他毒性更大的化学物质。许多临床试验正在使用干扰E2作用的药物。使用一种新的检测方法，我们将测量PAH患者血液中的E2及其代谢产物，并观察其如何随疾病严重程度、性别、年龄和肥胖而变化。我们还将检查患者肺部本身如何代谢E2。我们将在临床试验中分析患者的血液，以寻找影响E2的药物。我们将看到药物如何影响E2及其代谢，以及这与药物的治疗效果有何关系。我们将检查PAH患者的肺血管细胞，并检查E2及其代谢产物如何影响它们的生长和移动方式。我们还将研究PAH大鼠模型，以确定E2代谢在疾病发展过程中如何变化，以及受动物性别的影响。

项目成果

Serotonin and Pulmonary Hypertension; Sex and Drugs and ROCK and Rho.

血清素和肺动脉高压；

• DOI: 10.1002/cphy.c220004
• 发表时间: 2022
• 期刊: Comprehensive Physiology
• 影响因子: 5.8
• 作者: MacLean MR

Sex Differences in Pulmonary Hypertension.

• DOI: 10.1016/j.ccm.2020.10.005
• 发表时间: 2021-03
• 期刊: Clinics in chest medicine
• 影响因子: 5.7
• 作者: Hannah E Morris;N. Denver;R. Gaw;H. Labazi;K. Mair;M. MacLean

Notch3/Hes5 Induces Vascular Dysfunction in Hypoxia-Induced Pulmonary Hypertension Through ER Stress and Redox-Sensitive Pathways.

• DOI: 10.1161/hypertensionaha.122.20449
• 发表时间: 2023-08
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Morris HE;Neves KB;Nilsen M;Montezano AC;MacLean MR;Touyz RM
• 通讯作者: Touyz RM