Background: Obesity reshapes the cargo and bioactivity of adipose tissue-derived extracellular vesicles (adiposomes). Building on prior evidence that adiposomes from obese individuals disrupt endothelial caveolae, we investigated whether these vesicles directly alter endothelial Ca 2 + signaling and vascular ion channel function. Methods: Adiposomes were isolated from visceral fat of lean and obese donors and characterized by nanoparticle tracking analysis. Microvascular reactivity (flow- and acetylcholine-induced dilation) was measured in isolated small vessels from lean and obese donors, as well as in healthy microvessels after acute exposure to lean or obese adiposomes. Human microvascular endothelial cells were treated with lean or obese adiposomes to measure changes in intracellular Ca 2 + levels (Fluo-4 AM imaging) and ROS generation (CM-H 2 DCFDA fluorescence). Results: Small vessels from obese donors exhibited markedly reduced dilation responses to flow and acetylcholine. Short-term exposure of healthy microvessels to obese (but not lean) adiposomes similarly blunted vasodilation. Obese adiposomes greatly attenuated normal acetylcholine-evoked Ca 2 + "sparklets" in endothelial cells and substantially increased intracellular ROS. Obese adiposomes activated endothelial NADPH oxidase (NOX2), causing excess ROS that suppressed KATP channel activity and prevented normal KATP-mediated endothelial hyperpolarization; this in turn disrupted Ca 2 + –NO coupling and blunted microvascular dilation. Ongoing experiments will determine whether restoring endothelial KATP activity or removing NOX2-derived ROS can rescue Ca 2 + signaling and vasodilation, using approaches including pharmacological channel modulation, high-resolution Ca 2 + imaging, patch-clamp electrophysiology, and ex vivo human/mice arterioles. Implications: Targeting adiposome biogenesis/cargo or interrupting the NOX2–ROS–KATP axis may offer therapeutic strategies to reverse obesity-associated endothelial dysfunction and microvascular disease. 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.
Metwally et al. (Fri,) studied this question.