W119 - Peripheral Blood Mononuclear Cells from Patients with Systemic Lupus Erythematosus Induce Salt Sensitivity of Blood Pressure in Humanized Mice

Taseer Ahmad, PhD – Vanderbilt University Medical Center; Alexandria Haynes – Vanderbilt University Medical Center; Annet Kirabo – Vanderbilt University Medical Center; Amy Major – Vanderbilt University Medical Center; Michelle Ormseth – Vanderbilt University Medical Center; Charles Stein – Vanderbilt University Medical Center

Abstract Text: Systemic lupus erythematosus (SLE) is also a risk factor for cardiovascular disease (CVD) and hypertension. SLE and CVD are on the rise, and it is not known if this is attributable to the increased dietary salt in the modern diet and SSBP. We hypothesized that high salt intake increases both blood pressure and the proinflammatory milieu in mice humanized with the immune cells of patients with SLE. We humanized female NSG/MHCI/MHCII-/- immunodeficient mice with peripheral blood mononuclear cells (PBMCs) isolated from patients with SLE (n=5) and controls without autoimmune disease (n=4). The blood pressure was measured with radiotelemetry, immune phenotyping was performed with flow cytometry, and vascular reactivity was assessed in mesenteric arteries using wire myography after two weeks of a 4% high salt diet. High salt treatment significantly increased systolic blood pressure in lupus mice compared to the controls (135.5 vs. 123.8 mmHg, p=0.014). Antigen presenting cell infiltration (macrophages, monocytes, dendritic cells), their activation (CD86) and proinflammatory markers (IL-23 p19, TNF-alpha), and oxidative stress (Isolevuglandins, Nox2) were significantly higher in the kidneys of lupus mice. These mice exhibited vascular dysfunction (p < 0.05). Also, the lupus mice tended to excrete more albumin than the controls (17.24 vs. 25.89 µg/ml p=0.142), suggesting greater kidney injury. In conclusion, our findings suggest that immune cells from patients with SLE, in response to high salt intake, increase blood pressure and the proinflammatory milieu in the kidney, aorta, and spleen; impair vascular function; and worsen albuminuria in immunodeficient mice.