Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS, USA.
Physiol Rep. 2021 Feb;9(3):e14734. doi: 10.14814/phy2.14734.
Autoimmune diseases such as psoriasis, rheumatoid arthritis, and systemic lupus erythematosus (SLE) have high rates of hypertension and cardiovascular disease. Systemic lupus erythematosus is a prototypic autoimmune disorder that primarily affects women of childbearing age and is associated with a loss of self-tolerance, autoreactive B and T lymphocytes, and the production of autoantibodies, especially to nuclear components. In this study, we hypothesized that the pristane-inducible model of SLE would develop hypertension and vascular dysfunction as the disease progressed. To test this hypothesis, female C57BL/6 mice were administered PBS or pristane. Seven months after pristane administration, mice developed various autoantibodies, including anti-dsDNA IgG, anti-ssDNA IgG, and anti-nRNP IgG, as well as hypergammaglobulinemia. Several other immunological changes, including increased circulating neutrophils and increased CD4 CD8 (double negative) thymocytes were also detected. Mean arterial pressure (MAP) was elevated in pristane-treated mice when compared to PBS-treated mice. In addition, second-order mesenteric arteries from pristine-treated mice had impaired relaxation to the endothelium-dependent vasodilator acetylcholine compared to PBS-treated mice. These data suggest that the immune system dysfunction present in the pristane model of lupus contributes to the development of hypertension and vascular dysfunction.
自身免疫性疾病，如牛皮癣、类风湿关节炎和系统性红斑狼疮（SLE），高血压和心血管疾病的发病率很高。系统性红斑狼疮是一种典型的自身免疫性疾病，主要影响育龄妇女，与自身耐受性丧失、自身反应性 B 和 T 淋巴细胞以及自身抗体的产生有关，特别是针对核成分的自身抗体。在这项研究中，我们假设 pristane 诱导的 SLE 模型随着疾病的进展会发展为高血压和血管功能障碍。为了验证这一假设，我们给雌性 C57BL/6 小鼠注射 PBS 或 pristane。在 pristane 给药 7 个月后，小鼠产生了各种自身抗体，包括抗 dsDNA IgG、抗 ssDNA IgG 和抗 nRNP IgG，以及高丙种球蛋白血症。还检测到其他一些免疫变化，包括循环中性粒细胞增加和 CD4 CD8（双阴性）胸腺细胞增加。与 PBS 处理的小鼠相比，用 pristane 处理的小鼠的平均动脉压（MAP）升高。此外，与 PBS 处理的小鼠相比，来自 pristane 处理的小鼠的二级肠系膜动脉对内皮依赖性血管舒张剂乙酰胆碱的舒张功能受损。这些数据表明，狼疮 pristane 模型中存在的免疫系统功能障碍导致高血压和血管功能障碍的发展。
