In female mice, pristane-induced systemic lupus erythematosus worsened post-myocardial infarction cardiac remodeling and increased remote left ventricle CD3+ T cells (p<0.0001) at 56 days.
Does a pristane-induced SLE model worsen cardiac and renal injury following myocardial infarction in female mice?
Systemic lupus erythematosus worsens post-MI cardiac remodeling, pulmonary congestion, and renal inflammation in female mice, associated with an attenuated acute Type I interferon response.
In the United States, autoimmune diseases affect approximately 8% of the population, with an estimated 80% of that subset being women. Despite the increased prevalence, the relationship between autoimmune diseases, such as systemic lupus erythematosus (SLE), and myocardial infarction (MI) is poorly understood. In the present study, we hypothesized that cardiac function and tissue remodeling would be impaired following MI in a pristane-induced model of SLE. Adult female C57BL/6J mice received a single pristane injection 3 months before MI surgery. Permanent left coronary artery ligation was performed, and they were assessed at 7, 28, and 56 days post-MI. Cardiac function was evaluated pre- and post-surgery with echocardiography. Blood, kidney, and left ventricle (separated into infarct and remote zones) were collected for flow cytometry. Plasma IgG levels were assessed by ELISA. Left ventricle cytokines were detected using real-time PCR. Elevated plasma IgG levels confirmed the development of the SLE phenotype. At each time point, SLE mice exhibited decreased ejection fraction, increased left ventricle dilation (as determined by increased internal diameter at diastole and end-diastolic volume), and increased wall thinning. In addition, SLE mice had increased wet-lung weights at all time points, suggesting pulmonary congestion. At Day 7, SLE mice had increased relative percentages of left ventricle CD45+ cells (p=0.003), B cells (p=0.056), and circulating neutrophils (p=0.047). Expression of pro-inflammatory cytokines IL-6 and IL-18 was elevated in the infarct, while those of remodeling genes Col1a1 and Pecam1 were decreased. We also measured genes associated with the Type I interferon response in the left ventricle, showing an increased expression of Ifng, Ifna2, Ifnb1, Ifne, Ifnar1, Irf1, Irf2, Irf5, Irf7, and Irf9 in control mice but reduced expression in SLE mice. At D28, Irf1 remained decreased in the remote area (p=0.01), while Irf7 was increased (p=0.001); in the infarct area, Irf5 and Irf7 trended toward increased expression (p=0.07 for both genes), while Irf9 was increased (p=0.008). At Day 56, SLE mice had increased total CD45+ cells (p=0.03), CD3+ T cells (p< 0.0001), and CD8+ T cells (p=0.003) in the remote left ventricle, in addition to elevated kidney CD45+ cells (p=0.03), neutrophils (p=0.002), and monocytes (p< 0.0001). In the kidney, MI resulted in increased total CD45+ cells, T cells, monocytes, and neutrophils, whereas SLE showed increased kidney neutrophil expansion (p=0.01). In conclusion, SLE is associated with more severe post-MI outcomes, including impaired cardiac remodeling and inflammation, pulmonary congestion, and renal inflammation. These effects are associated with an attenuated acute Type I Interferon response in the heart. Funding sources: AHA Career Development Award (Mouton) – CDA856365; NHLBI R01 (Mouton) – HL166737; NIH R00 (Taylor) – HL146888; NIH U54 (Taylor) – HL169191; UMMC Intramural Support Program (Mouton/Taylor) 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.
O'Quinn et al. (Fri,) conducted a other in Systemic lupus erythematosus and myocardial infarction. Pristane-induced systemic lupus erythematosus model vs. Control mice was evaluated on Cardiac function, tissue remodeling, and inflammation post-myocardial infarction. In female mice, pristane-induced systemic lupus erythematosus worsened post-myocardial infarction cardiac remodeling and increased remote left ventricle CD3+ T cells (p<0.0001) at 56 days.