Xin Jiechen, Xu Zhibin, Zhang Feng, Sun Yue, Wang Xiaoyan, Wu Chaojun, Zhao Longshu
Department of Critical Care Medicine, Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China.
Department of Organ Transplantation, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Medicine (Baltimore). 2025 Mar 7;104(10):e41771. doi: 10.1097/MD.0000000000041771.
This study assesses the causal effects of antihypertensive and lipid-lowering drugs on inflammatory cytokines using a Mendelian randomization (MR) approach. We conducted a drug-targeted MR analysis using data from large-scale genome-wide association studies and eQTL datasets. SNPs near drug target genes served as instrumental variables to investigate the impact of antihypertensive (angiotensin-converting enzyme inhibitors [ACEIs], ARBs) and lipid-lowering drugs (HMGCR inhibitors, proprotein convertase subtilisin/Kexin type 9 [PCSK9] inhibitors, Niemann-Pick C1-like 1 inhibitors) on inflammatory cytokines. Sensitivity analyses, including leave-one-out and MR-Egger tests, were performed to confirm the robustness of the findings. ACEIs were associated with decreased levels of IL-1β, TNF-α, and CRP. ARBs did not show significant effects on inflammatory cytokines. HMGCR inhibitors significantly reduced MCP-1, MIP-1β, TNF-α, and IFN-γ, while PCSK9 inhibitors were linked to reductions in IL-1β and IL-6. Sensitivity analyses supported the reliability of these findings. The study demonstrated distinct anti-inflammatory effects of ACEIs, HMGCR inhibitors, and PCSK9 inhibitors. These findings support the potential use of these drugs to mitigate inflammation-related complications in patients with chronic conditions.
本研究采用孟德尔随机化（MR）方法评估降压药和降脂药对炎性细胞因子的因果效应。我们利用大规模全基因组关联研究和eQTL数据集的数据进行了药物靶向MR分析。药物靶基因附近的单核苷酸多态性（SNPs）作为工具变量，以研究降压药（血管紧张素转换酶抑制剂[ACEIs]、血管紧张素Ⅱ受体阻滞剂[ARBs]）和降脂药（3-羟基-3-甲基戊二酰辅酶A还原酶[HMGCR]抑制剂、枯草溶菌素/克新9型前蛋白转化酶[PCSK9]抑制剂、尼曼-匹克C1样1抑制剂）对炎性细胞因子的影响。进行了敏感性分析，包括留一法和MR-Egger检验，以确认研究结果的稳健性。ACEIs与白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和C反应蛋白（CRP）水平降低有关。ARBs对炎性细胞因子未显示出显著影响。HMGCR抑制剂显著降低单核细胞趋化蛋白-1（MCP-1）、巨噬细胞炎性蛋白-1β（MIP-1β）、TNF-α和干扰素-γ（IFN-γ），而PCSK9抑制剂与IL-1β和白细胞介素-6（IL-6）水平降低有关。敏感性分析支持了这些研究结果的可靠性。该研究证明了ACEIs、HMGCR抑制剂和PCSK9抑制剂具有明显的抗炎作用。这些研究结果支持了使用这些药物减轻慢性病患者炎症相关并发症的可能性。
