Peroxisome proliferator activated receptor-γ agonist pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus

作者：Sarfaraz Hasni, Yenealem Temesgen‐Oyelakin, Michael A. Davis, Jun Chu, Elaine Poncio, Mohammad Naqi, Sarthak Gupta, Xinghao Wang, Christopher B. Oliveira, Dillon Claybaugh, Amit K. Dey, Shajia Lu, Philip M. Carlucci, Monica Purmalek, Zerai Manna, Yinghui Shi, Isabel Ochoa-Navas, Jinguo Chen, Amrita Mukherjee, Kyu Lee Han, Foo Cheung, Galina Koroleva, Yasmine Belkaid, John S. Tsang, Richard Apps, Donald E. Thomas, Theo Heller, Massimo Gadina, Martin P. Playford, Xiaobai Li, Nehal N. Mehta, Mariana J. Kaplan · 发表于：Annals of the Rheumatic Diseases · 年份：2022 · DOI：10.1136/ard-2022-222658 · 被引用次数：25 · 研究领域：Systemic Lupus Erythematosus Research、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Peroxisome Proliferator-Activated Receptors

OBJECTIVES: Premature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases. We hypothesised that PGZ could improve vascular dysfunction and cardiometabolic parameters in SLE. METHODS: Eighty SLE subjects with mild to severe disease activity were randomised to a sequence of PGZ followed by placebo for 3 months, or vice versa, in a double-blind, cross-over design with a 2-month wash-out period. Primary endpoints were parameters of endothelial function and arterial inflammation, measured by multimodal assessments. Additional outcome measures of disease activity, neutrophil dysregulation, metabolic disturbances and gene expression studies were performed. RESULTS: Seventy-two subjects completed the study. PGZ was associated with a significant reduction in Cardio-Ankle Vascular Index (a measure of arterial stiffness) compared with placebo. Various metabolic parameters improved with PGZ, including insulin resistance and lipoprotein profiles. Circulating neutrophil extracellular trap levels also significantly decreased with PGZ compared with placeb...