《一种高选择性mPGES-1抑制剂在血管紧张素小鼠模型中阻断腹主动脉瘤进展》

  • 来源专题:重大疾病防治
  • 编译者: 蒋君
  • 发布时间:2024-03-25
  • 腹主动脉瘤(AAA)是一种致命的、永久性的主动脉瘤。药理学和遗传学研究指出,包括微粒体前列腺素E2合成酶-1(mPGES-1)在内的多种蛋白质是潜在的有前景的靶点。然而,在动物模型中,mPGES-1抑制剂的给药是否能有效减弱AAA的进展仍不得而知。目前还没有美国食品药品监督管理局批准的AAA药物治疗方法。目前的研究强调了抗炎药靶点和可翻译性的重要性。值得注意的是,mPGES-1是一种诱导型酶,负责前列腺素E2(PGE2)的过量产生,前列腺素E2是一种众所周知的主要促炎前列腺素。在这里,我们首次证明了高选择性mPGES-1抑制剂(UK4b)可以完全阻断ApoE?/?血管紧张素(Ang)II小鼠模型中AAA的进一步生长。我们的研究结果表明,使用像UK4b这样的mPGES-1抑制剂作为AAA的介入治疗及其潜在的临床应用前景广阔。
  • 原文来源:https://www.nature.com/articles/s41598-024-57437-9?error=cookies_not_supported&code=1b3a6c9b-e1ae-4387-9afc-a666e3a0ea81
相关报告
  • 《腹主动脉瘤的更新指南》

    • 来源专题:心血管疾病防治
    • 编译者:张燕舞
    • 发布时间:2018-05-22
    • 2018年2月,美国血管外科学会(SVS)发布了关于腹主动脉瘤(AAA)患者护理的最新指南。 与先前指南的主要区别包括较长的超声监视小AAA的间隔时间,使用血管质量计划围手术期死亡风险评分来辅助选择性AAA的决策制定,并且当解剖学适合时,血管内而不是开放性AAA破裂修复,包括快速 如果急诊科能够在90分钟内完成手术干预,则转移至血管中心。 我们的建议与这些修订是一致的。 BACKGROUND Decision-making related to the care of patients with an abdominal aortic aneurysm (AAA) is complex. Aneurysms present with varying risks of rupture, and patient-specific factors influence anticipated life expectancy, operative risk, and need to intervene. Careful attention to the choice of operative strategy along with optimal treatment of medical comorbidities is critical to achieving excellent outcomes. Moreover, appropriate postoperative surveillance is necessary to minimize subsequent aneurysm-related death or morbidity. METHODS The committee made specific practice recommendations using the Grading of Recommendations Assessment, Development, and Evaluation system. Three systematic reviews were conducted to support this guideline. Two focused on evaluating the best modalities and optimal frequency for surveillance after endovascular aneurysm repair (EVAR). A third focused on identifying the best available evidence on the diagnosis and management of AAA. Specific areas of focus included (1) general approach to the patient, (2) treatment of the patient with an AAA, (3) anesthetic considerations and perioperative management, (4) postoperative and long-term management, and (5) cost and economic considerations. RESULTS Along with providing guidance regarding the management of patients throughout the continuum of care, we have revised a number of prior recommendations and addressed a number of new areas of significance. New guidelines are provided for the surveillance of patients with an AAA, including recommended surveillance imaging at 12-month intervals for patients with an AAA of 4.0 to 4.9 cm in diameter. We recommend endovascular repair as the preferred method of treatment for ruptured aneurysms. Incorporating knowledge gained through the Vascular Quality Initiative and other regional quality collaboratives, we suggest that the Vascular Quality Initiative mortality risk score be used for mutual decision-making with patients considering aneurysm repair. We also suggest that elective EVAR be limited to hospitals with a documented mortality and conversion rate to open surgical repair of 2% or less and that perform at least 10 EVAR cases each year. We also suggest that elective open aneurysm repair be limited to hospitals with a documented mortality of 5% or less and that perform at least 10 open aortic operations of any type each year. To encourage the development of effective systems of care that would lead to improved outcomes for those patients undergoing emergent repair, we suggest a door-to-intervention time of <90 minutes, based on a framework of 30-30-30 minutes, for the management of the patient with a ruptured aneurysm. We recommend treatment of type I and III endoleaks as well as of type II endoleaks with aneurysm expansion but recommend continued surveillance of type II endoleaks not associated with aneurysm expansion. Whereas antibiotic prophylaxis is recommended for patients with an aortic prosthesis before any dental procedure involving the manipulation of the gingival or periapical region of teeth or perforation of the oral mucosa, antibiotic prophylaxis is not recommended before respiratory tract procedures, gastrointestinal or genitourinary procedures, and dermatologic or musculoskeletal procedures unless the potential for infection exists or the patient is immunocompromised. Increased utilization of color duplex ultrasound is suggested for postoperative surveillance after EVAR in the absence of endoleak or aneurysm expansion. CONCLUSIONS Important new recommendations are provided for the care of patients with an AAA, including suggestions to improve mutual decision-making between the treating physician and the patients and their families as well as a number of new strategies to enhance perioperative outcomes for patients undergoing elective and emergent repair. Areas of uncertainty are highlighted that would benefit from further investigation in addition to existing limitations in diagnostic tests, pharmacologic agents, intraoperative tools, and devices.
  • 《腹主动脉瘤中的破骨细胞:一种新的治疗靶点》

    • 来源专题:重大新药创制—研发动态
    • 编译者:杜慧
    • 发布时间:2017-10-09
    • 腹主动脉瘤(AAA)是造成死亡的主要原因。目前,AAA治疗的主要手段是手术修复,FDA未批准AAA疗法。科研工作者正在进行大量的研究,以发现新的AAA疗法。 AAA的病理生理学被认为是为使动脉瘤壁退化的炎症和蛋白水解过程之间复杂的相互作用。在AAA中可观察到动脉钙化,但其程度低于动脉闭塞性疾病中的动脉钙化。成骨细胞样细胞与动脉粥样硬化斑块中的矿物质沉积有关。最近,在动脉粥样硬化斑块中发现了破骨细胞样细胞 - 成骨细胞的分解代谢物。此外,破骨细胞样细胞存在于AAA的壁中,但不存在于健康主动脉中。破骨细胞样细胞分泌基质金属蛋白酶(MMP)-蛋白酶可能有助于动脉瘤壁的退化。通过降低MMPs来抑制破骨细胞样细胞或许可预防动脉瘤进展。在本篇综述中,我们将讨论AAA形成的病理生理学和药物治疗在AAA治疗中的当前作用。此外,我们强调了破骨细胞在AAA的发展中的关键作用,并讨论了抑制破骨细胞的疗法。