Exercise training responses in lupus-prone MRL-lpr mice

Endothelial dysfunction, a precursor of overt cardiovascular disease (CVD), is more prevalent in patients with systemic lupus erythematosus (SLE) compared to healthy controls, even in the absence of known CVD. Exercise can improve endothelial dysfunction. However, evidence for cardiovascular adaptations to exercise training in SLE patients is minimal and varied. Therefore, the purpose of this study was to determine the efficacy of exercise training to prevent endothelial dysfunction in lupus-prone mice. It was hypothesized that moderate-intensity exercise would prevent a decline in endothelial function when initiated before the onset of disease. For this study, female lupus-prone MRL-lpr mice were used. MRL-lpr (lpr) mice are homozygous for the lympho-proliferation spontaneous mutation (Faslpr). Disease onset begins at 12 weeks of age in females, and progression is rapid, making them a valuable model of SLE. Nine-week-old lpr mice completed an exercise performance test and were randomly assigned to exercise-training (EX, n = 6) or sedentary control (SED, n = 6) groups. EX mice completed 8 weeks of exercise training at 60% of maximal workload. At the end of the training period, a second exercise performance test was completed. Concentration-response curves to the endothelium-dependent vasorelaxant acetylcholine (ACh) were generated in thoracic aorta from 17- to 20-week-old exercise-trained (EX) and sedentary control (SED) lpr mice, and aged-matched healthy control MRL/MpJ (MpJ, n = 6) mice to assess endothelial function. Exercise capacity was significantly reduced in SED and EX groups. However, the decline in exercise capacity was significantly attenuated in EX mice (SED = -18.6 ± 1.8 min; EX = -11.4 ± 3.2 min, P = 0.004). Furthermore, only 3 of 6 SED mice were able to complete the post-training performance test, whereas all EX mice completed the test. In SED mice, maximal responses to ACh were ~25% lower than MpJ, confirming endothelial dysfunction in MRL-lpr mice. Responses were ~15% higher in aorta from EX mice compared to SED, reflecting improved endothelial function. Endothelium-independent responses to sodium nitroprusside (SNP) were not different across groups. Spleen weight and spleen weight-to-body weight ratio were assessed as markers of disease progression. Spleen weights were significantly lower in EX mice compared to SED (SED = 844.2 ± 287.7 mg vs. EX = 500.7 ± 239.5 mg, P = 0.0001). Spleen weights from MpJ mice (98.7 ± 6.4 mg) were significantly smaller than those of both EX and SED groups. As with spleen weight, spleen weight to body weight ratios were also significantly different across groups (P < 0.0001). The smaller spleen size in EX mice compared to SED mice implies that exercise training attenuated splenomegaly in lpr mice. Collectively, these data suggest that moderate intensity exercise training can improve endothelial function and attenuate disease progression in lupus-prone MRL-lpr mice. Supported by the Texas Tech University Research Assistance Program This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.