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Jak2V617f突变激活中性粒细胞mTOR–HIF-1α 通路，驱动脂质代谢重编程在动脉粥样硬化中...

創建於：2025年12月24日

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問題

Jak2V617f突变激活中性粒细胞mTOR–HIF-1α 通路，驱动脂质代谢重编程在动脉粥样硬化中的机制及干预研究帮我找足够的文献作为理论基础支撑

回答

为了帮助你更准确地寻找相关文献，能否请你补充以下信息：

  1. 你希望文献聚焦在哪一类研究？（例如：基础机制研究、动物模型、临床研究或药物干预等）
  2. 是否有时间范围要求？例如近5年、近10年等。
  3. 你是否只需要中文文献，还是也包括英文文献？
  4. 是否对期刊级别有要求？（如SCI收录、核心期刊等）

请提供这些信息，我将据此展开深入的文献查找工作。

問題

Jak2V617F突变与动脉粥样硬化；JAK2/mTOR/HIF-1∂通路的激活机制；中性粒细胞、NETs形成与免疫代谢；等多种维度支撑我的假说，只要英文的，1区文献

思考

Organizing literature review

I'm organizing a structured literature review to confirm the necessity of each step in mapping out Jak2V617F-induced atherosclerosis and lipid metabolism pathways, including sources.

Investigating atherosclerosis

I'm piecing together various studies on clonal hematopoiesis, including JAK2V617F mutation and its impact on atherosclerosis. Also exploring interventions like JAK2 and mTOR inhibitors.

Gathering data

OK, let's look at JAK2, mTOR, and HIF-1α pathways, focusing on NET inhibitors, anti-inflammatory therapy, and lipid metabolism. This includes 25-40 references from authoritative sources like PubMed.

Initiating a focused search
I'm starting to explore recent studies on JAK2 V617F, particularly its impact on neutrophil metabolic pathways like mTOR/HIF-1α, glycolysis, and lipid metabolism.

Examining key studies

I’m reviewing sources like a 2024 Cell & Bioscience journal focused on neutrophil-specific JAK2-V617F expression's impact on metabolic and adhesive phenotypes. Also, I’m searching for details on Sci Transl Med 2018;10:eaan8292 regarding thrombosis promotion by JAK2V617F mutant neutrophils.

Gathering evidence

I’m consolidating atherosclerosis-specific evidence by referring to a 2018 Taxol study. Additionally, the 2022 and 2024 JCI articles and the 2019 Circulation Research article are being reviewed for further insights.

Refining the search

I'm narrowing down to the title "Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease" or "Clonal Hematopoiesis and Blood-Cancer Risk" from NEJM 2017, looking for authors like Jaiswal et al.

Pulling together research

I'm piecing together details on mTOR-HIF-1α in immune cells, particularly neutrophils, and their link to atherosclerosis and NETs. Progress is steady and promising.

Considering neutrophil roles

Neutrophils are likely involved in oxidized LDL processing and NET production in atherosclerosis, as indicated by recent literature.

Spotting key papers

I found a crucial Blood 2012 paper and a Cardiovascular Research 2023 paper. Each one enriches our understanding of mTOR–HIF-1α, NET formation, and their roles in atherosclerosis. For complete insights, further literature review is essential.

Locating relevant research

I'm searching for key papers that explore the role of neutrophil extracellular traps (NETs) in promoting atherosclerosis, including those by the Soehnlein group and others, to enhance our understanding of this process.

Connecting elements

OK, let me see: linking neutrophil extracellular traps, cholesterol crystals, and cytokine production in atherosclerosis. The role of PAD4 and NETosis in plaque erosion is also interesting.

Mapping JAK2 signaling

I'm exploring how JAK2V617F interacts with mTOR and HIF-1α, and its influence on neutrophil metabolism and NETosis. This leads me to the cross-talk with PI3K/AKT/mTOR.

Mapping connections

I’m working through sources to link JAK2V617F with the PI3K/Akt/mTOR and HIF-1 pathways. This involves reviewing abstracts from journals like Nature Leukemia and Frontiers in Immunology to ensure high-quality citations.

Refining literature recommendations

I'm working through refining the literature recommendations, including a core set of Q1 original studies and reviews, and optional additional references for a comprehensive understanding.

Acquiring details

I'm gathering specifics from the JCI 2025 article to pull together authors, year, DOI, and any figures needed for accurate citation.

Reviewing JCI article

OK, let's see—I'm noting low-allele-burden mice and their atherosclerosis. It’s interesting to see the interplay of MERTK and TREM2 with NETs alongside IL-1 signaling, suggesting key therapeutic mechanisms.

Analyzing current research

I’m detailing mechanistic studies on atherosclerosis, focusing on Jak2V617F's role, including macrophage inflammation, erythrophagocytosis, and the impact of Jak2V617F in clonal hematopoiesis on plaque instability and endothelial injury.

Synthesizing insights

I’m gathering theoretical support and literature on JAK2V617F, immunometabolism, and neutrophil metabolism to form a conceptual framework linking atherosclerosis, NETosis, and inflammatory responses.

Piecing together research

I’m integrating IL-1β and JAK inhibition with QoL theory, considering HIF-1α's role in macrophage atherosclerosis. Clinical trials like CANTOS and COLCOT support IL-1β and JAK inhibition strategies. Progressing towards a comprehensive theoretical framework.

Piecing together citations

I’m gathering 30-40 key references on neutrophil lipid metabolism, mTOR/HIF-1, and JAK2V617F neutrophil-specific expression. Europe PMC and existing sources will ensure balanced citations.

Examining connections

I’m gathering info on NETs and their link to IL-1β, ceramides, cholesterol trafficking, and HIF-1α. This includes studying references from Circulation Research, Cardiovasc Res 2023, and JLR 2024.

Reviewing immunometabolism

I’m mapping out key studies on metabolic regulation in neutrophils, focusing on histone H4, HIF-1α stabilization, JAK2-V617F, and the JAK2-mTOR-HIF pathway. These topics are crucial for understanding immunometabolism.

Pulling together references

I'm thinking through aligning the retrieved references with the user's needs. This approach should streamline integrating them into the existing framework.

Gathering detailed insights

OK, let me see. The analysis is checking the detailed output from turn3, including the Sci Transl Med eaan8292 paper.

Ensuring accurate citations

I’m mapping out citations for each paper's findings, ensuring they're formatted correctly and listed at the end of bullet lines. It’s interesting to see the focus on accurately attributing sources.

Gathering references

I'm collecting literature on JAK2V617F and atherosclerosis risk, including reviews and meta-analyses, while focusing on critically acclaimed articles like JCI 2024 review and AHA 2024 review.

Consulting academic sources

Listing references with authorship and publication details. Ensuring accuracy and avoiding unsupported claims. Progressing through this process to provide a credible, reliable list.

Evaluating scientific rigor

I’m pulling together a list of 25-30 scientific papers with reliable sources, avoiding ungrounded information and focusing on the most current and pertinent research available.

Studying NETosis

I’m examining mitochondrial ROS' role in promoting HIF-1 in neutrophils. Researchers show cholesterol-driven NETosis in atherosclerotic plaques through IL-1β secretion.

Sifting through research

I'm examining reviews on tumor models and experimental methods. The search history reflects a blend of tumor biology, therapy mechanisms, and innovative models. I’m piecing together tumor microenvironment insights too.

Investigating final sources

I’m piecing together details on JAK2V617F and neutrophil expression differences, citing Science Translational Medicine 2018 and J Hematol Oncol 2024. This wraps up our comprehensive search.

Mapping Q1 sources

I’m identifying Q1 journals for literature, like NEJM, Science, and Nature. Each list entry will be categorized, annotated, and cited from these prestigious sources.

Addressing thrombosis and plaque erosion

I'm pulling together thrombosis and plaque erosion, touching on mTOR-HIF-1 from Blood 2012. Next, integrating HIF-1 in macrophages and atherosclerosis.

Focusing on specific proteins

Pulling together insights on JAK2, PI3K/AKT/mTOR, HIF-1α, and lipid metabolism, I’m organizing recent high-impact English papers to highlight their roles in neutrophils and NETs.

Laying out the options

I'm gathering core references on JAK2V617F and related interventions. This involves selective cytokine labelling and EEF2 immunofluorescence for context.

Highlighting key research

I'm examining how NETosis is triggered by cholesterol and IL-1β, and how JAK2V617F in neutrophils influences NETs and thrombosis.

Verifying article details

Checking the article details in "N Engl J Med" 2017, avoiding quoting hazard ratios from memory without citing them, and planning to avoid giving exact numbers unless sourced.

Tracking JCI patterns

I'm exploring the JCI article ID and DOI patterns to possibly locate the DOI for the JCI 182939 article. This involves examining previous outputs and manually checking for the DOI in initial lines.

Identifying relevant DOIs

I’m gathering DOIs for articles like "European Heart Journal 2025" and "Science Translational Medicine 2018." For "Blood 2012," I'm noting the focus on mTOR and NET formation.

Assessing sources

I'm highlighting "Mammalian target of rapamycin regulates neutrophil extracellular trap formation" for its relevance. Including DOI can enhance trust.

Listing influential articles

Laying out crucial papers on JAK2V617F connections to atherosclerosis, covering human genetics/epidemiology and causal mouse mechanistic links.

Piecing together research

I’m gathering findings on IL-1β, NETs, and their roles in atherosclerosis. Nih policies cast a spotlight on essential references like Liu et al., Fidler TP et al., etc.

Mapping out connections

I'm linking JAK2V617F venous thrombosis to integrin activation, which supports the integrin-mediated adhesion mechanism. This aligns with the cited JCI 2017 article.

Piecing together intervention strategies

Mapping out potential interventions includes PAD4 inhibitors or deficiency, mTOR inhibitors like rapamycin, and lipid metabolic reprogramming, using relevant citations to ensure clarity and precision.

Assessing lipid metabolism roles

I'm evaluating Q1 papers on HIF-1's influence on lipid metabolism and mTORC1's role in lipid synthesis, seeking relevant references for incorporating into the review.

Identifying key sources

I'm gathering information on mTORC1, HIF-1, and lipid metabolic reprogramming. Theoretical sections without citations and a few Q1 papers were included.

Charting lipid impacts

Neutrophils undergoing the JAK2V617F mutation exhibit notable changes that probably involve oxidative burst and energy metabolism, hinting at a connection with lipid metabolism via "lipid axis."

Supporting hypothesis

I’m planning to provide 25 solid literature references, mostly from Q1 journals, to back the hypothesis with studies on Jak2V617F mutation in ASCVD risk, atherosclerosis, and thrombosis.

Crafting the final answer

I’m pulling together a comprehensive "minimum set" of 20 essential Q1 papers and an expanded selection of Q1 reviews and mechanistic studies. Citations will be formatted in Chinese per guidelines.

Consulting multiple sources

I'm gathering info on PAD4, NETosis, cholesterol, and thrombosis. Considering various journal articles for a thorough understanding. Progress is steady, and I'm aiming for accuracy throughout the research.

Piecing together data

Refining and synthesizing information for accuracy and coherence.

Reasoned for 8m 5s

回答

下面按你提出的假说主线，把“JAK2V617F → 中性粒细胞 mTOR–HIF‑1α → 免疫代谢/脂质代谢重编程 → NETs → 动脉粥样硬化/斑块易损与糜烂/血栓”的证据链拆开，并给出足够支撑每一环的英文、偏JCR Q1的核心文献（优先 NEJM / Nature / Science / Blood / Circulation* / Eur Heart J / JCI / Cardiovascular Research / JTH / Nat Rev Cardiol 等）。

说明：Q1分区会随年份与学科类别变化，我选的是通常长期处于顶刊/一区的期刊；你最终投标或写作时建议用 JCR/SCImago 再核对分区。

你假说最关键的“可被文献支撑的命题”拆解

命题1：JAK2V617F（CHIP/低等位基因负荷也可）是ASCVD/MI强风险因子，并与斑块糜烂等机制相关

  • 人群层面：CHIP 与冠心病/缺血性卒中/死亡风险增加；其中 JAK2V617F 通常被认为是效应量最大之一（相较DNMT3A/TET2等）。(Europe PMC)
  • 机制层面更细化：JAK2V617F 与MI的“斑块糜烂 vs 破裂”分型关联已有专门病例-对照研究。(OUP Academic)

命题2：JAK2V617F 在动物模型中可“因果性”加重动脉粥样硬化，并通过炎症小体/IL‑1轴与细胞互作推动斑块不稳定

  • 经典因果模型：造血系统表达 Jak2V617F 会促进早期病变与晚期复杂化，涉及巨噬细胞炎症、红细胞吞噬/清除缺陷等。(Europe PMC)
  • AIM2–IL‑1β轴：Jak2V617F 巨噬细胞的增殖/糖酵解代谢、复制压力与 AIM2炎症小体可加重动脉粥样硬化；阻断IL‑1β可改善坏死核心、纤维帽等稳定性指标。(Europe PMC)
  • 低负荷突变也能“点火”：仅少量 Jak2V617F 细胞就可通过 IL‑1介导的突变细胞→野生型细胞炎症串扰，导致吞噬受体（MERTK/TREM2）下降、NETs增加、斑块更不稳定；并且提供了“稳定MERTK/TREM2”的干预思路。(JCI)

命题3：中性粒细胞/NETosis 是把“突变造血→血管事件”的效应放大的关键执行者之一，且与脂质环境、IL‑1和炎症小体形成正反馈

  • NETs推动动脉粥样硬化炎症：胆固醇晶体可诱导NET形成，NET可“许可/priming”巨噬细胞产生IL‑1β并放大炎症级联（Science经典）。(Europe PMC)
  • 脂质驱动的“巨噬细胞→中性粒细胞”串扰：巨噬细胞胆固醇蓄积可通过 IL‑1β 促进斑块内NETosis，并可被IL‑1β中和抗体或NLRP3抑制剂抑制。(OUP Academic)
  • 斑块糜烂相关的NET靶向证据：PAD4缺失或DNase I破坏NET可减少“类似糜烂”的内皮损伤/去内皮。(AHA Journals)
  • AIM2也与“晚期斑块易损”相关：dsDNA–AIM2炎症小体参与晚期斑块易损性调控。(AHA Journals)

命题4：mTOR–HIF‑1α 是中性粒细胞NET形成与免疫代谢的核心控制轴，可作为你提出“JAK2V617F→mTOR–HIF‑1α→代谢重编程→NETs”的机制底盘

  • 关键直接证据：mTOR可通过调控HIF‑1α表达来调节人中性粒细胞NET形成（Blood经典）。(ASH Publications)
  • 中性粒细胞代谢综述（写理论框架非常好用）：mTOR、HIF‑1α与AMPK等被系统性梳理为影响中性粒细胞效应功能（含NET）的代谢调控节点。(OUP Academic)
  • 你的“JAK2V617F与NET易感”衔接点：JAK2V617F背景下，血小板–中性粒细胞协同可增强NETosis；DNase/阿司匹林等对NET/血栓有抑制效应，为“干预研究”提供抓手。(ScienceDirect)

10–15篇“必读核心文献”——直接拼出你的理论主链条

  1. Jaiswal et al., NEJM 2017 — Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease（CHIP与ASCVD风险关联的奠基性人群证据，写引言必引）。(Europe PMC)

  2. Wang et al., Circulation Research 2018 — Macrophage inflammation, erythrophagocytosis, and accelerated atherosclerosis in Jak2(V617F) mice（Jak2V617F造血表达促进粥样硬化、炎症、清除缺陷等因果证据）。(Europe PMC)

  3. Fidler et al., Nature 2021 — The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis（Jak2V617F→增殖/糖酵解→复制压力→AIM2炎症小体→斑块更坏；IL‑1β阻断可稳定斑块）。(Europe PMC)

  4. Campbell & Li et al., JCI 2024 — Inflammatory crosstalk impairs phagocytic receptors and aggravates atherosclerosis in clonal hematopoiesis in mice（低负荷Jak2V617F即可通过IL‑1串扰导致NETs↑、MERTK/TREM2↓、斑块不稳定；并提供TREM2激动剂/稳定MERTK的干预范式）。(JCI)

  5. Liu et al., JCI 2022 — Erythroid lineage Jak2V617F expression promotes atherosclerosis through erythrophagocytosis and macrophage ferroptosis（把“脂质过氧化/铁死亡”与Jak2V617F‑ASCVD连接起来，帮你写“脂质代谢/铁死亡”维度）。(JCI)

  6. Warnatsch et al., Science 2015 — Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis（胆固醇晶体→NET→巨噬IL‑1β/Th17放大，NET与脂质炎症的经典桥梁）。(Europe PMC)

  7. Yalcinkaya et al., Cardiovascular Research 2023 — Cholesterol accumulation in macrophages drives NETosis in atherosclerotic plaques via IL‑1β secretion（脂质蓄积→IL‑1β→NETosis的“细胞间串扰”因果证据；IL‑1β抗体/NLRP3抑制剂可抑制NET）。(OUP Academic)

  8. Franck et al., Circulation Research 2018 — Roles of PAD4 and NETosis in Experimental Atherosclerosis and Arterial Injury（PAD4缺失/DNase I 对“糜烂相关内皮损伤”有效，是你做干预实验的重要依据）。(AHA Journals)

  9. McInturff et al., Blood 2012 — mTOR regulates neutrophil extracellular trap formation via induction of HIF‑1α（直接把 mTOR–HIF‑1α 与 NETosis 挂钩，是你假说“核心通路”必引）。(ASH Publications)

  10. European Heart Journal 2025 — Plaque erosion risk and JAK2 V617F variant（把JAK2V617F与斑块糜烂机制直接关联，利于你把结局从“斑块面积”升级为“事件机制/糜烂-血栓”）。(OUP Academic)

  11. International Journal of Cardiology 2024 — The clonal hematopoiesis mutation Jak2V617F aggravates endothelial…（聚焦“糜烂/内皮损伤—NET”方向的JAK2V617F机制文章，与你题目高度贴合）。(International Journal of Cardiology)

  12. Blood 2024（Regular article） — Jak2V617F clonal hematopoiesis promotes arterial thrombosis via platelet activation and cross talk（人群meta + 小比例克隆模型；强调血小板‑中性粒细胞互作、动脉血栓，适合做“干预靶点：抗血小板/抑NET”论证）。(ASH Publications)

  13. Journal of Thrombosis and Haemostasis 2023 — 血小板与中性粒细胞协同增强NETosis；阿司匹林降低NET标志物、DNase抑制血栓（非常适合“干预研究”章节）。(ScienceDirect)

  14. Leukemia 2019 — HIF‑1 is a new therapeutic target in JAK2V617F-positive cells（证明在JAK2V617F背景下HIF‑1可作为药靶；帮助你把HIF‑1从“现象”提升到“可干预”。）(Nature)

  15. Nat Rev Cardiol 2023（comment） — Clonal haematopoiesis and atherosclerotic cardiovascular disease（可作为你写引言/讨论的“总览型一区综述”，并串联CANTOS、TET2/JAK2模型等）。(Nature)

按主题补齐的“支撑文献库”——用于写每一段理论基础

A. JAK2V617F‑CHIP/MPN 与动脉粥样硬化/血栓事件

  • JCI 2024 review：CHIP与动脉粥样硬化的机制、潜在靶向策略（可用于你在引言里把“CHIP→炎症→ASCVD”框架讲清楚）。(JCI)
  • JAK2突变CH与血栓（Blood 2024 UK Biobank等）：JAK2‑mutant CHIP 与静脉血栓关联（说明JAK2突变克隆具有系统性促凝/促炎表型）。(ASH Publications)

B. “炎症小体–IL‑1轴”在JAK2V617F相关粥样硬化中的中心作用

  • Nature 2021 AIM2（上面已列）：Jak2V617F→AIM2→IL‑1β是强机制链条。(Europe PMC)
  • Cardiovascular Research 2023：脂质（胆固醇蓄积）→IL‑1β→NETosis，并可被IL‑1β抗体/NLRP3抑制剂阻断。(OUP Academic)
  • Science 2015 Warnatsch：NET→巨噬IL‑1β priming；形成正反馈。(Europe PMC)

C. 中性粒细胞/NETs 与“斑块不稳定、糜烂、血栓”

  • Circulation Research 2018 PAD4/DNase：NET靶向更像影响“糜烂/内皮损伤/血栓”而非早期脂纹面积——与你将结局聚焦“斑块糜烂/血栓”非常契合。(AHA Journals)
  • Atherosclerosis（2025，综述/更新）：NETs作为动脉粥样硬化与卒中驱动因素，包含胆固醇晶体、NLRP3、DAMPs等机制图谱（适合写综述背景）。(ScienceDirect)
  • JCI Insight：NETs促进巨噬炎症小体活化等（用来补“NET→炎症小体”的互作证据）。(JCI Insight)

D. mTOR–HIF‑1α：NET形成 + 免疫代谢的“枢纽通路”

  • Blood 2012（mTOR→HIF‑1α→NET）：最直接的“通路因果”证据。(ASH Publications)
  • J Leukoc Biol 2024 review：中性粒细胞代谢调控全景（mTOR/HIF‑1α/AMPK等）+ 潜在可靶向性。(OUP Academic)
  • Frontiers Immunology 2016：低氧/稳定HIF‑1α可增强（某些条件下）细胞外陷阱形成（帮助你写“斑块缺氧微环境 + HIF‑1α”）。(Frontiers)

E. “脂质代谢重编程”如何嵌入你的链条

你要把“脂质代谢重编程”写得站得住，一般需要两类文献拼起来：
(1) 斑块脂质环境如何驱动中性粒细胞NET/炎症；(2) mTOR/HIF‑1α作为代谢重编程中枢。

  • 斑块脂质环境→NET/IL‑1：Cardiovascular Research 2023（胆固醇蓄积→IL‑1β→NETosis）是你在“脂质→NET”这段最硬的一篇。(OUP Academic)
  • TREM2作为“脂质/脂蛋白感受器”并关联斑块稳定：JCI 2024 里明确把 TREM2（脂质/脂蛋白激活的吞噬受体） 放进Jak2V617F‑CH串扰与纤维帽修复通路中，能帮你把“脂质代谢/吞噬受体/斑块稳定”三者串起来。(JCI)
  • Jak2V617F与“脂质过氧化/铁死亡”：JCI 2022 红系Jak2V617F→巨噬铁死亡（脂质过氧化核心机制）→粥样硬化加重，为你写“脂质代谢异常/脂质过氧化”提供高强度支撑。(JCI)
  • mTOR与HIF‑1α的代谢耦联（为你写“mTOR上游—HIF‑1α翻译/蛋白累积”提供通路背景）：JBC关于Akt/mTOR促进HIF‑1α蛋白合成的机制证据可用作“通路耦合”的补充。(JBC)

F. 干预研究的“可落地靶点”与对应文献依据（你题目需要）

这里把“你能做/能写”的干预，按靶点归类，并给出对应支撑文献：

  1. IL‑1轴（IL‑1β、IL‑1R）
  • Jak2V617F‑CH模型中，IL‑1信号是突变细胞→WT细胞串扰与NETs的关键；Il1r1缺失可逆转多项不稳定表型。(JCI)
  • 脂质蓄积驱动NETosis同样可被IL‑1β中和抗体抑制。(OUP Academic)
  • 临床层面“炎症干预降低事件”的标杆：CANTOS（canakinumab，抗IL‑1β）常用于论证“IL‑1轴可降低残余炎症风险”（用于你讨论“转化潜力”）。(Nature)
  1. 炎症小体（AIM2 / NLRP3）
  • Jak2V617F‑CH：AIM2炎症小体是核心驱动；遗传或药理干预可减轻动脉粥样硬化与坏死核心、提高纤维帽稳定性。(Europe PMC)
  • 斑块脂质诱导NETosis：NLRP3抑制剂可阻断IL‑1β介导的NETosis。(OUP Academic)
  1. NET靶向（PAD4 / DNase）
  • PAD4缺失或DNase I可降低糜烂相关内皮损伤/去内皮。(AHA Journals)
  • 在JAK2V617F相关血栓/NET互作模型中，DNase可逆转部分血栓表型（支持你写“NET作为治疗靶点”）。(ScienceDirect)
  1. 血小板–中性粒细胞互作 / 抗血小板策略
  • JAK2V617F背景下血小板与中性粒细胞协同增强NETosis；阿司匹林降低NET标志物、减少血栓（“廉价可转化干预”）。(ScienceDirect)
  • Jak2V617F‑CH动脉血栓的系统性研究（Blood 2024）也强调“platelet activation and cross talk”。(ASH Publications)
  1. mTOR / HIF‑1α
  • mTOR–HIF‑1α直接调控NET形成（为你做rapamycin类药理学验证提供依据）。(ASH Publications)
  • HIF‑1作为JAK2V617F背景潜在药靶（Leukemia 2019），支持你把“HIF‑1抑制剂/基因干预”写进干预策略。(Nature)
  1. 吞噬受体稳定化（MERTK/TREM2）—“斑块稳定化”型干预
  • JCI 2024给出非常清晰的干预范式：
    • 非可切割MERTK改善坏死核心/纤维帽
    • TREM2激动抗体（4D9）显著增加纤维帽并消除对照与Jak2VF差异
      这对你写“精准医学/斑块稳定化”特别有价值。(JCI)

你可以直接用来写“理论基础”章节的结构建议（按你题目最顺的写法）

  1. CHIP与ASCVD：从流行病学到因果模型（NEJM 2017 + Nat Rev Cardiol综述）(Europe PMC)
  2. JAK2V617F为何“更危险”：炎症小体/IL‑1轴 + 细胞串扰（Nature 2021 + JCI 2024）(Europe PMC)
  3. 中性粒细胞与NETs：把炎症与血栓事件连接起来（Science 2015 + Circulation Research 2018 PAD4/DNase）(Europe PMC)
  4. 免疫代谢枢纽：mTOR–HIF‑1α驱动NET与代谢重编程（Blood 2012 + J Leukoc Biol 2024 review）(ASH Publications)
  5. 脂质代谢重编程如何落点到中性粒细胞/斑块微环境（Cardiovasc Res 2023 + JCI 2022 ferroptosis + JCI 2024 TREM2）(OUP Academic)
  6. 干预策略与可验证假说（IL‑1/AIM2/NLRP3、PAD4/DNase、抗血小板、mTOR/HIF‑1等）(OUP Academic)

给你可复制到PubMed/Scopus的检索式（帮助你继续扩充“一区英文文献”）

你现在已经有“必读核心文献”，接下来扩充最好按模块检索（每个模块各抓 20–50 篇，最终筛成你要的Q1）：

  • JAK2V617F & atherosclerosis
    ("JAK2V617F" OR "JAK2 V617F") AND (atherosclerosis OR "plaque erosion" OR "myocardial infarction")

  • JAK2V617F & neutrophils / NETs
    ("JAK2V617F" OR "myeloproliferative neoplasm") AND (neutrophil OR NETosis OR "neutrophil extracellular trap*")

  • mTOR–HIF‑1α & NETosis
    (mTOR OR "mechanistic target of rapamycin") AND ("HIF-1alpha" OR HIF1A) AND (NETosis OR "extracellular trap*")

  • Immunometabolism & neutrophil lipid metabolism
    (neutrophil AND (immunometabolism OR "metabolic reprogramming") AND (lipid OR cholesterol OR fatty acid))

  • Inflammasome–IL‑1 & NETs in atherosclerosis
    (atherosclerosis AND (AIM2 OR NLRP3 OR inflammasome OR "interleukin-1") AND (NETosis OR neutrophil))

再加上筛选：Journal: top quartile/Q1（如果数据库支持）+ Article type: Research/Review + Last 10 years（或你需要的范围）。

如果你愿意，我也可以在下一步把以上文献进一步整理成你论文/基金申请常用的“证据矩阵”（每篇文献对应：模型/样本、关键发现、与假说哪一环对应、可借鉴的方法学与可干预靶点），并给出一套可实验验证的关键指标面板（中性粒细胞mTORC1活性、HIF‑1α蛋白、脂代谢通路读出、NET标志物、斑块糜烂相关内皮损伤指标等）。

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