Myeloperoxidase impacts vascular function by altering perivascular adipocytes’ secretome and phenotype in obesity
Year: 2025
Type: article
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. • MPO is associated with endothelial dysfunction in obese patients • MPO induces pro-inflammatory PVAT activation and immune cell abundance • MPO suppresses PVAT beiging via sGC-β1 inhibition, thereby reducing oxygen consumption • MPO is a potential therapeutic target to prevent cardiovascular disease in obesity Hof et al. show that myeloperoxidase (MPO) links obesity to vascular dysfunction by driving perivascular adipose tissue (PVAT) inflammation. MPO levels correlate with body weight and endothelial dysfunction, while MPO deficiency reduces PVAT inflammation, promotes adipocyte “beiging” via sGC-β1, increases adiponectin secretion, and improves vascular function.
Source: Cell Reports Medicine
Authors: 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
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
OpenAlex ID: W4409583797