Myeloperoxidase impacts vascular function by altering perivascular adipocytes' secretome and phenotype in obesity.

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-04-10 DOI:10.1016/j.xcrm.2025.102087

Alexander Hof, Max Landerer, Philipp Peitsmeyer, Ronja Herzog, Jens Alber, Maysam Ahdab, Felix Sebastian Nettersheim, Dennis Mehrkens, Simon Geißen, Simon Braumann, Henning Guthoff, Philipp von Stein, Harshal Nemade, Felix Simon Ruben Picard, Ramona Braun, Friedrich Felix Hoyer, Jens Claus Brüning, Alexander Pfeifer, Staffan Hildebrand, Holger Winkels, Stephan Baldus, Matti Adam, Jasper Schäkel, Martin Mollenhauer

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Abstract

Obesity, a main driver of cardiovascular morbidity, contributes to endothelial dysfunction and inflammation in adipose tissues. Perivascular adipose tissue (PVAT) surrounds arteries and influences vascular function. In obesity, immune cells, including myeloperoxidase (MPO)-releasing myeloid cells, accumulate in PVAT. In this study, we show MPO levels to correlate with body weight and endothelial function in obese patients (n = 33) and mice. In addition, MPO deficiency reduces immune cell frequency, enhances PVAT beiging via soluble guanylyl cyclase β1 (sGC-β1), and increases oxygen consumption in vivo. Further, nitrotyrosine formation and inflammatory cytokine release are attenuated in obese Mpo^-/- mice. Mechanistically, adiponectin (APN) secretion improves endothelial function and reduces arterial stiffness. In vitro, MPO-treated human white adipocytes show lower APN and brown adipocyte marker expression but increased inflammation. Thus, MPO impairs vascular function via PVAT inflammation and suppression of vasoprotective mediators, making it a potential therapeutic target in obesity-related cardiovascular disease.

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髓过氧化物酶通过改变肥胖患者血管周围脂肪细胞的分泌组和表型来影响血管功能。

肥胖是心血管疾病的主要驱动因素，有助于脂肪组织的内皮功能障碍和炎症。血管周围脂肪组织（PVAT）包围着动脉并影响血管功能。在肥胖中，免疫细胞，包括髓过氧化物酶（MPO）释放髓样细胞，在PVAT中积累。在这项研究中，我们发现肥胖患者（n = 33）和小鼠的MPO水平与体重和内皮功能相关。此外，MPO缺乏降低免疫细胞频率，通过可溶性guanyyl环化酶β1 （sGC-β1）增强PVAT生成，并增加体内耗氧量。此外，肥胖Mpo-/-小鼠的硝基酪氨酸形成和炎症细胞因子释放减弱。从机制上讲，脂联素（APN）的分泌可以改善内皮功能，减少动脉僵硬。在体外，mpo处理的人白色脂肪细胞APN和棕色脂肪细胞标志物表达降低，但炎症增加。因此，MPO通过PVAT炎症和抑制血管保护介质损害血管功能，使其成为肥胖相关心血管疾病的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.