Renal TLR-7/TNF-a pathway as a potential female-specific mechanism in the pathogenesis of autoimmune-induced hypertension
Renal TLR-7/TNF-a pathway as a potential female-specific mechanism in the pathogenesis of autoimmune-induced hypertension
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DOI：
10.1152/ajpheart.00286.2022
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发表时间：
2022-12-01
影响因子：
4.8
通讯作者：
Mathis, Keisa W.
中科院分区：
文献类型：
--
作者：
Chaudhari, Sarika;D'Souza, Bradley M.;Mathis, Keisa W.
高血压在系统性红斑狼疮（SLE）患者中很常见。当前研究的目标是追踪 SLE 中高血压和肾损伤的发病机制，确定发病机制，并强调性别之间疾病发展的差异。使用留置动脉导管在 34-35 周龄的清醒雄性和雌性 SLE (NZBWF1) 和对照 (NZW) 小鼠中测量平均动脉压。肾损伤、肾炎症和肾血流动力学的测量用于监测潜在性别差异的潜在因素。雄性和雌性 SLE 小鼠在 35 周龄时均出现高血压，并且雌性的高血压与肾损伤有关，但雄性则不然。 Toll 样受体 (TLR)-7 是 SLE 肾脏病理学的已知贡献者，其下游效应物促炎细胞因子肿瘤坏死因子 (TNF)-a 在雄性 SLE 小鼠中的含量低于雌性。雄性 SLE 小鼠也比雌性小鼠具有更高的肾小球滤过率 (GFR) 和更低的肾血管阻力 (RVR)。我们的数据表明，尽管雌性 SLE 小鼠的高血压与肾脏机制相关，但雄性 SLE 小鼠的高血压可能与肾脏变化无关。未来的研究将继续剖析治疗患有潜在慢性炎症和/或自身免疫的高血压患者时应考虑的性别特异性因素。新的和值得注意的 男性和女性 SLE 中高血压的患病率很高；然而，雄性 SLE 小鼠患有高血压，但没有肾脏受累。雌性 SLE 小鼠高血压的发生以肾脏为中心，与 TLR-7->TNF-a 通路等肾脏损伤机制密切相关。性别之间发病机制的这种明显差异可能会对我们如何治疗患有潜在慢性自身免疫/炎症性疾病的高血压患者产生重大影响。
Hypertension is prevalent in patients with systemic lupus erythematosus (SLE). The goal of the current study is to track the pathogenesis of hypertension and renal injury in SLE, identify contributory mechanisms, and highlight differences in disease development among sexes. Mean arterial pressure was measured in conscious male and female SLE (NZBWF1) and control (NZW) mice at 34-35 wk of age using indwelling arterial catheters. Measures of renal injury, renal inflammation, and renal hemodynamics were used to monitor the potential contributors to latent sex differences. Both male and female SLE mice were hypertensive at 35 wk of age, and the hypertension was linked to renal injury in females, but not in males. A known contributor of renal pathology in SLE, Toll-like receptor (TLR)-7, and its downstream effector, the proinflammatory cytokine tumor necrosis factor (TNF)-a, were lower in male SLE mice than in females. Male SLE mice also had higher glomerular filtration rate (GFR) and lower renal vascular resistance (RVR) than females. Our data suggest that although hypertension in female SLE mice is associated with renal mechanisms, hypertension in male SLE mice may develop independent of renal changes. Future studies will continue to dissect sex-specific factors that should be considered when treating patients with hypertension with underlying chronic inflammation and/or autoimmunity. NEW & NOTEWORTHY There is a high prevalence of hypertension in male and female SLE; however, male SLE mice are hypertensive without renal involvement. The development of hypertension in female SLE mice is renocentric and strongly associated with injurious renal mechanisms like the TLR-7->TNF-a pathway. This clear difference in the pathogenesis among the sexes could have a significant impact on how we treat patients with hypertension with underlying chronic autoimmune/inflammatory diseases.