William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Center for Inflammation and Therapeutic Innovation, Queen Mary University of London, London, UK.
Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, USA.
EBioMedicine. 2023 Mar;89:104468. doi: 10.1016/j.ebiom.2023.104468. Epub 2023 Feb 13.
Persons with HIV (PWH) have an increased risk of cardiovascular disease (CVD) compared to HIV-seronegative individuals (SN). Inflammation contributes to this risk but the role of lipid mediators, with central roles in inflammation, in HIV infection remain to be established; further aspirin reduces CVD risk in the general population through production of some of these anti-inflammatory lipid mediators, but they have not been studied in PWH.
We evaluated the relationship between plasma lipid mediators (i.e. 50 lipid mediators including classic eicosanoids and specialized pro-resolving mediators (SPMs)) and HIV status; and the impact of aspirin in PWH on regulating these autacoids. Plasma samples were obtained from 110 PWH receiving antiretroviral therapy (ART) from a randomized trial of aspirin (ACTG-A5331) and 107 matched SN samples (MACS-WIHS Combined Cohort).
PWH had lower levels of arachidonic acid-derived pro-inflammatory prostaglandins (PGs: PGE and PGD) and thromboxanes (Tx: TxB), and higher levels of select pro-resolving lipid mediators (e.g. RvD4 and MaR2) compared to SN. At the interval tested, aspirin intervention was observed to reduced PGs and Tx, and while we did not observe an increase in aspirin triggered mediators, we observed the upregulation of other SPM in aspirin treated PWH, namely MaR2.
Together these observations demonstrate that plasma lipid mediators profiles, some with links to systemic inflammation and CVD risk, become altered in PWH. Furthermore, aspirin intervention did not increase levels of aspirin-triggered pro-resolving lipid mediators, consistent with other reports of an impaired aspirin response in PWH.
NIH.
与 HIV 血清阴性个体（SN）相比，HIV 感染者（PWH）患心血管疾病（CVD）的风险增加。炎症导致了这种风险，但脂质介质在 HIV 感染中的作用仍有待确定；此外，阿司匹林通过产生一些抗炎脂质介质来降低普通人群的 CVD 风险，但尚未在 PWH 中进行研究。
我们评估了血浆脂质介质（即包括经典类二十烷酸和专门的促解决介质（SPM）在内的 50 种脂质介质）与 HIV 状态之间的关系；以及阿司匹林对 PWH 调节这些自分泌酶的影响。从阿司匹林（ACTG-A5331）随机试验中获得了 110 名接受抗逆转录病毒治疗（ART）的 PWH 和 107 名匹配的 SN 样本（MACS-WIHS 联合队列）的血浆样本。
与 SN 相比，PWH 中花生四烯酸衍生的促炎前列腺素（PG：PGE 和 PGD）和血栓烷（Tx：TxB）水平较低，选择性促解决脂质介质（如 RvD4 和 MaR2）水平较高。在测试的时间间隔内，观察到阿司匹林干预可降低 PG 和 Tx，虽然我们没有观察到阿司匹林触发的介质增加，但我们观察到阿司匹林治疗的 PWH 中其他 SPM 的上调，即 MaR2。
这些观察结果表明，PWH 的血浆脂质介质谱发生了改变，其中一些与全身炎症和 CVD 风险有关。此外，阿司匹林干预并没有增加阿司匹林触发的促解决脂质介质的水平，这与其他关于 PWH 中阿司匹林反应受损的报告一致。
NIH。
Zotero 插件
