Seasonal travel stressors impact the development of hypertension in female lupus mice
Authors: Dinh Viet , Chaudhari Sarika , Gusson Shimoura Almeida Lima Caroline , Young-Stubbs Cassandra , Mathis Keisa 
Published: May 2023

Hypertension is the leading risk factor for cardiovascular morbidity and mortality, and growing evidence implicates chronic renal inflammation as a culprit in the development of hypertension, such as in the case of the autoimmune disease systemic lupus erythematosus (SLE). Our lab uses the established female NZBWF1 mouse model of SLE to mechanistically link renal inflammation to development of hypertension. Mice are typically shipped to our university young (6 weeks), develop autoantibodies as adults (~20 weeks), and are hypertensive by 35 weeks. We observed that mice shipped while young in summer months have higher renal cortical heat shock protein (HSP)90 immediately upon arrival compared to those shipped in winter. Summer mice also have higher autoantibodies and albuminuria in adulthood than winter mice. These findings suggest that seasonal and environmental factors like heat, compounded by travel stress, act as early life stressors that adversely affect disease progression in these mice. However, it is unknown how seasonal travel stressors affect HSP90, SLE disease progression, and blood pressure in mice exposed as adults rather than in early life. We aim to study if seasonal factors affect adult-traveling mice differently and if HSP90 is associated with these differences. We hypothesize that summer travel will upregulate HSP90 in adult female lupus mice, leading to increases in disease severity and blood pressure compared to winter mice. Female NZBWF1 mice were shipped in either summer or winter at 18–19 weeks. At 35 weeks, mice were implanted with carotid catheters to assess mean arterial pressure (MAP) for two days. Mice were euthanized, with blood and kidneys collected to assess plasma double-stranded (ds)DNA autoantibodies as well as plasma and renal levels of HSP90. Adult-shipped mice developed heightened dsDNA autoantibodies (5.4e5±5.8e4 vs. 3.8e5±5.5e4 U/mL; P=0.0423; n=13–19), plasma HSP90 (36.42±6.41 vs. 21.59±2.29 pg/mL; P=0.0082; n=15–20), and renal cortical HSP90 (0.16±0.02 vs. 0.03±0.01 pg/μg; P<0.0001; n=11–17) at 35 weeks compared to young-shipped mice. Among adult-traveling mice, summer mice developed heightened dsDNA autoantibodies compared to winter mice (7.0e5±9.7e4 vs. 3.3e5±6.3e4 U/mL; P=0.0012; n=6–7). Summer mice also had higher plasma HSP90 (57.57±8.00 vs. 17.92±1.10 ng/mL; P<0.0001; n=7), but no differences in renal cortical HSP90 (0.16±0.04 vs. 0.17±0.03 ng/μg; P=0.9885; n=5–6). Crucially, adult-traveling summer mice also had higher blood pressure compared to winter mice (136±3 vs. 129±2 mmHg; P=0.0339; n=5–7). In conclusion, these findings indicate that severity of autoimmunity and hypertension in female SLE mice may be dependent on the season and age in which mice are shipped and changes in HSP90. Future studies will further investigate HSP90’s role in renal inflammation and hypertension by modulating its expression in SLE mice and a kidney-specific knockout model.

NIH (K01HL139869, R01HL153703), Departmental Seed Grant, and Department of Defense (LR210096)

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.