《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
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  • 《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.
  • 《血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂在COVID-19中的应用:证据评估》

    • 来源专题:新发突发疾病(新型冠状病毒肺炎)
    • 编译者:蒋君
    • 发布时间:2020-05-21
    • 背景:基于血管紧张素转换酶抑制剂(ACEIs)和血管紧张素受体阻滞剂(ARBs)在COVID-19患者中可能会提高SARS-CoV-2受体ACE2表达的假设,人们对此安全性提出了关注。方法:我们对实验动物和人类受试者(n=11)的研究(n=12)进行了文献回顾,并评估了ACEIs和ARBs对ACE2表达影响的证据。我们优先研究评估ACE2蛋白表达数据,直接测量或从ACE2活性分析推断。结果:动物实验结果与ACEIs或ARBs治疗后ACE2表达增加不一致。对照/假动物在多个研究中几乎没有效果。那些报道ACE2表达增加的研究往往涉及急性损伤模型和/或比通常给患者使用的剂量更高。来自人类研究的数据绝大多数暗示给药ACEIs/ARBs不会增加ACE2的表达。结论:现有证据,特别是人类研究的数据,不支持使用ACEI/ARB增加ACE2表达和COVID-19并发症风险的假设。我们的结论是,接受ACEIs和ARBs治疗的患者应继续将其用于经批准的适应症。