Sex Differences in the Development of Hypertension in the Setting of Autoimmunity




Morales, Jessica
D'Souza, Bradley
Mathis, Keisa W.
Young-Stubbs, Cassandra M.


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Purpose: Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease associated with high risks of hypertension. We previously confirmed the disease develops later in life in male SLE mice compared to females (35 vs.< 30 weeks). We also found that both male and female SLE mice are hypertensive by 35 weeks and that this hypertension is linked to renal injury in females but not males; therefore, we aimed to investigate potential contributors to the latent sex difference. Toll-like receptor 7 (TLR7) is an immune mediator active in autoimmunity that instigates widespread tissue damage. We hypothesized that increased TLR7 promotes renal injury in female SLE mice and a different mechanism, potentially increased renal vascular resistance (RVR), is responsible for the hypertension in male SLE mice. Methods: Renal cortical expression of TLR7 was assessed via Western blot in male and female SLE mice (NZBWF1) at 35 weeks. Renal blood flow and mean arterial pressure were measured in anesthetized male and female SLE mice to determine RVR. Results: Female SLE mice had higher (p< 0.05) expression of TLR7 (2.6e6 ±5.4e5; normalized to total protein) than males (1.7e6 ± 3.3e5). Male SLE mice had lower RVR than females (5.15 ±0.60 vs. 10.07 ±1.23 mmHg·min·kg·mL-1). Conclusion: Our data suggest that while the hypertension in female SLE mice may be due to renal mechanisms, male SLE mice develop hypertension through other mechanisms. Future studies will continue to dissect sex-specific factors that should be considered when treating hypertensive patients with underlying chronic inflammation.