Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas.
Am J Physiol Heart Circ Physiol. 2022 Dec 1;323(6):H1331-H1342. doi: 10.1152/ajpheart.00286.2022. Epub 2022 Nov 11.
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 () and control () 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)-α, 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. 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-α 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.
高血压在系统性红斑狼疮（SLE）患者中很常见。本研究的目的是跟踪 SLE 患者高血压和肾脏损伤的发病机制，确定促成机制，并强调性别间疾病发展的差异。使用留置动脉导管在 34-35 周龄的清醒雄性和雌性 SLE（）和对照（）小鼠中测量平均动脉压。使用肾脏损伤、肾脏炎症和肾脏血液动力学的测量来监测潜在的性别差异发展的促成因素。35 周龄时，雄性和雌性 SLE 小鼠均患有高血压，且这种高血压与雌性小鼠的肾脏损伤有关，但与雄性小鼠无关。Toll 样受体（TLR）-7 及其下游促炎细胞因子肿瘤坏死因子（TNF）-α 是 SLE 肾脏病理学的已知促成因素，在雄性 SLE 小鼠中低于雌性。雄性 SLE 小鼠的肾小球滤过率（GFR）也高于雌性，而肾血管阻力（RVR）则低于雌性。我们的数据表明，尽管雌性 SLE 小鼠的高血压与肾脏机制有关，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在治疗患有潜在慢性炎症和/或自身免疫性疾病的高血压患者时应考虑的性别特异性因素。男性和女性 SLE 患者中高血压的患病率都很高；然而，雄性 SLE 小鼠患有高血压而没有肾脏受累。雌性 SLE 小鼠高血压的发生以肾为中心，与 TLR-7→TNF-α 通路等损伤性肾脏机制密切相关。这种性别间发病机制的明显差异可能对我们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。
