In the process of physiological cardiac repair, splenic leukocyte-activated lipoxygenases (LOXs) are essential for the biosynthesis of specialized pro-resolving lipid mediators as a segment of an active process of acute inflammation in splenocardiac manner. In contrast, young 12/15LOX^−/− mice use a compensatory mechanism that amplifies epoxyeicosatrienoic acid mediators after myocardial infarction, improving cardiac repair, function, and survival. Next, we tested whether deletion of 12/15LOX impacted the genesis of chronic inflammation in progressive aging. To test the risk factor of aging, we used the inter-organ hypothesis and assessed heart and spleen leukocyte population along with the number of inflammation markers in age-related 12/15LOX^−/− aging mice (2 months, 6 months, 13 months) and compared with C57BL/6 J (WT; wild type) as controls (2 months). The 12/15LOX^−/− aging mice showed an age-related increase in spleen mass (hypersplenism) and decreased marginal zone area. Results suggest increased interstitial fibrosis in the heart marked with the inflammatory mediator (PGD₂) level in 12/15LOX^−/− aging mice than WT controls. From a cellular perspective, the quantitative measurement of immune cells indicates that heart and spleen leukocytes (CD11b⁺ and F4/80⁺ population) were reduced in 12/15LOX^−/− aging mice than WT controls. At the molecular level, analyses of cytokines in the heart and spleen suggest amplified IFN-γ, with reduced COX-1, COX-2, and ALOX5 expression in the absence of 12/15LOX-derived mediators in the spleen. Thus, aging of 12/15LOX^−/− mice increased spleen mass and altered spleen and heart structure with activation of multiple molecular and cellular pathways contributing to age-related integrative and inter-organ inflammation.

在生理性心脏修复过程中，脾白细胞激活的脂氧合酶 (LOX) 对于专门的促分解脂质介质的生物合成是必不可少的，它是脾心方式急性炎症活动过程的一部分。相比之下，年轻的 12/15LOX ^-/-小鼠使用一种补偿机制，在心肌梗塞后放大环氧二十碳三烯酸介质​​，从而改善心脏修复、功能和存活率。接下来，我们测试了 12/15LOX 的缺失是否会影响进行性衰老中慢性炎症的发生。为了测试衰老的危险因素，我们使用了器官间假说并评估了心脏和脾脏白细胞数量以及年龄相关 12/15LOX ^{-/-中炎症标志物的数量}衰老小鼠（2 个月、6 个月、13 个月）并与 C57BL/6 J（WT；野生型）作为对照（2 个月）进行比较。12/15LOX ^-/-衰老小鼠表现出与年龄相关的脾脏质量增加（脾功能亢进）和边缘区面积减少。结果表明，在 12/15LOX ^-/-衰老小鼠中，与 WT 对照相比，以炎症介质 (PGD ₂ ) 水平为标志的心脏间质纤维化增加。从细胞的角度来看，免疫细胞的定量测量表明，与WT 对照相比，12/15LOX ^{-/-衰老小鼠的心脏和脾脏白细胞（CD11b +}和 F4/80 ⁺群）减少。在分子水平上，对心脏和脾脏中细胞因子的分析表明扩增IFN-γ，在脾脏中不存在 12/15LOX 衍生介质的情况下， COX-1、COX-2和ALOX5表达降低。因此，12/15LOX ^-/-小鼠的衰老增加了脾脏质量并改变了脾脏和心脏结构，激活了多种分子和细胞途径，导致与年龄相关的综合性和器官间炎症。