The Role of Thromboxane A2 in Vascular Regulation in Women with Endometriosis

血栓素 A2 在子宫内膜异位症女性血管调节中的作用

• 批准号: 10750782
• 负责人: Auni Williams
• 金额: $ 4.7万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10750782
• 关键词: Acceleration; Affect; Atherosclerosis; Blood Platelets; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Development; Diffuse; Endothelial Cells; Endothelium; Enzymes; Event; Exercise; Gynecologic; Impairment; Inflammation; Lesion; Mediating; Nitric Oxide; Nitric Oxide Synthase; Pain; Patients; Physiological; Play; Population; Pre-Clinical Model; Reflex action; Regulation; Research; Risk Factors; Role; Sensory; Skeletal Muscle; Stimulus; Thromboxane A2; Training; Translating; Uterus; Vascular Smooth Muscle; Vasoconstrictor Agents; Vasodilation; Vasomotor; Woman; antagonist; cardiovascular disorder risk; chronic pain; cyclooxygenase 2; endometriosis; endothelial dysfunction; pharmacologic; pre-doctoral; prevent; preventive intervention; receptor; systemic inflammatory response; vasoconstriction

Project Summary CVD is the leading cause of death worldwide. Endometriosis has been repeatedly identified as an independent risk factor for CVD that affects an estimated one in ten women in the world. Endometriosis is a gynecologic condition characterized by invasive extrauterine endometriotic lesions, chronic pain and pain sensitization, and systemic inflammation and is associated with accelerated cardiovascular disease risk. The expression of cyclooxygenase-2, a key enzyme in inflammation, is upregulated in endometriotic lesions as are its metabolites, namely TxA2. TxA2 is a potent vasoconstrictor able to diffuse across the endothelium to act directly on its receptors in the vascular smooth muscle. TxA2 can also antagonize NOS within the endothelial cells, preventing vasodilation. A decrease in nitric oxide (NO)-mediated vasodilation defines endothelial dysfunction and is regarded as a critical early event in the development of atherosclerosis and overt cardiovascular disease. Women with endometriosis demonstrate marked endothelial dysfunction compared with healthy controls. Furthermore, TxA2 receptors (TP) play a key role in sensitizing the sensory afferents in skeletal muscle in pre- clinical models of cardiovascular disease, leading to an exaggerated exercise pressor reflex. This is a strong predictor of major adverse cardiovascular events in cardiovascular disease patients. Therefore, the purpose of this project is twofold: 1) to determine the effect of the TP on the regulation of microvascular function and in circulating platelets in women with endometriosis and 2) to investigate sensory afferent sensitization in women with endometriosis. We hypothesize that women with endometriosis demonstrate exaggerated vasoconstriction to both pharmacological stimuli locally modulating vasomotor tone and to physiological sympathoexcitatory stimuli. This project and associated training plan will serve as a vehicle for exceptional predoctoral training for the candidate.

项目摘要 心血管疾病是世界范围内主要的死亡原因。子宫内膜异位症已被反复确认为一种独立的 据估计，世界上十分之一的女性都有心血管疾病的危险因素。子宫内膜异位症是妇科疾病 以侵袭性子宫内膜异位病变、慢性疼痛和疼痛敏感化为特征的情况，以及 全身性炎症，并与心血管疾病风险加速相关。的表达方式 环氧合酶-2是炎症中的关键酶，在子宫内膜异位症病变中表达上调，其代谢产物也是如此。 即TXA2。TXA2是一种强大的血管收缩物质，能够扩散到内皮细胞，直接作用于它的 血管平滑肌中的受体。TXA2还可以拮抗内皮细胞内的一氧化氮合酶，防止 血管扩张。一氧化氮(NO)介导的血管扩张功能下降定义了内皮功能障碍 被认为是动脉粥样硬化和显性心血管疾病发展的关键早期事件。 与健康对照组相比，子宫内膜异位症患者表现出明显的内皮功能障碍。 此外，血栓素A2受体(TP)在增敏骨骼肌感觉传入中起着关键作用。 心血管疾病的临床模型，导致运动加压反射的夸大。这是一个很强的 心血管疾病患者主要不良心血管事件的预测因子。因此，其目的是 这个项目有两个方面：1)确定茶多酚对微血管功能的调节作用 子宫内膜异位症患者的循环血小板及2)女性感觉传入敏感度的研究 患有子宫内膜异位症。我们假设患有子宫内膜异位症的女性表现出过度的血管收缩。 对局部调节血管舒缩张力的药物刺激和对生理交感兴奋的作用 刺激物。该项目和相关的培训计划将作为一种特殊的博士前培训工具 候选人。