Abstract 075: Sex Differences in the Development of Autoimmune-Associated Hypertension

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder with prevalent hypertension and is a novel disease model to study the link between chronic inflammation and hypertension. Because SLE is female-dominant, studies are usually conducted in female NZBWF1 mice, a well-established model of SLE. However, men are also diagnosed with SLE and the late onset and different clinical features draws interest. We hypothesize that sex differences exist in SLE and that female SLE mice have heightened disease, hypertension, and renal injury earlier than males. Female and male SLE and control ( NZW ) mice were monitored for albuminuria starting at 30 weeks of age and then at 35 weeks implanted with vascular catheters to allow measurement of blood pressure in conscious mice. At 30 weeks, female SLE mice had elevated plasma dsDNA autoantibodies, the hallmark of SLE, compared to male SLE (4.6e5 ± 1.3e5 vs. 6.3e4 ± 2.7e4 U/mL; n=3-5; all p<0.05), female controls (8.9e4 ± 3.3e4), and male controls (4.8e4 ± 9.3e3). At this same time point, 32% (7 out of 22) of female SLE mice had albuminuria versus 5% (1 out of 20) of male SLE, 5% (1 out of 22) of female controls, and no male controls. Although male SLE mice did not reach similar levels of dsDNA autoantibodies as SLE females (2.0e5 ± 4.6e4 vs. 3.9e5 ± 4.3e4; n=8-13; p=0.015), by 35 weeks, the autoantibodies were increasing in SLE males (2.0e5 ± 4.6e4 vs. 6.3e4 ± 2.7e4; p=0.157) and higher than male controls (4.3e4 ± 9.3e3; p=0.046). At 35 weeks, 63% (10 out of 16) of female SLE mice had albuminuria versus 5% (1 out of 19) of male SLE, 5% (1 out of 22) of female controls, and no male controls. Importantly, both female and male SLE mice were hypertensive at 35 weeks: blood pressure was higher in female SLE than female controls (152 ± 5 vs. 126 ± 3 mmHg; n=6-8; p=0.003) and in male SLE compared to male controls (152 ± 4 vs. 136 ± 4 mmHg; n=6-11; p=0.041). These data confirm the development of hypertension and renal injury in female SLE mice and suggest that male SLE mice develop hypertension with no renal involvement. Future studies will allow us to investigate the divergent mechanisms involved in autoimmune-induced hypertension in female and male mice, which will ultimately provide clues in sex differences in hypertensive humans with underlying chronic inflammation.