BMC Seminar - Molecular Responses in Endothelial Dysfunction

BMC Seminar Thursday 24 September at 12:00 in Árnagarður, room 301

Spearker: Arnar Ingi Vilhjálmsson, PhD student of Óttar Rolfsson, Faculty of Medicine, University of Iceland

Title: Molecular Responses in Catecholamine-Induced Endothelial Dysfunction

Abstract: Endothelial dysfunction is a common feature of acute critical illness and is associated with adverse outcomes. Despite the diverse causes of critical illness, excessive sympathoadrenal activation and elevated circulating catecholamines are frequently observed and have been proposed as contributors to endothelial injury through the shock-induced endotheliopathy (SHINE) framework. However, the direct effects of sustained catecholamine exposure on endothelial cells and the molecular mechanisms underlying these responses remain incompletely understood. Previous work from our group demonstrated that catecholamine exposure induces metabolic activation, glycocalyx loss, and impaired endothelial barrier function. Building on these findings, we investigated the molecular response to sustained catecholamine exposure in human lung microvascular endothelial cells using functional assays together with transcriptomic and proteomic profiling. Catecholamine exposure induced barrier dysfunction and metabolic activation accompanied by dynamic, time-dependent molecular remodeling involving metabolic, oxidative stress, and lipid-associated processes. GRAMD1B emerged as a persistent and dose-responsive feature of the response, while regulatory analyses identified MYC-associated remodeling across early and sustained responses. Pharmacological inhibition further identified β₂-adrenergic signaling as an important upstream contributor to these molecular changes. Together, these findings characterize a coordinated endothelial response to sustained catecholamine exposure and identify β₂-adrenergic signaling, GRAMD1B, and MYC-associated regulation as components of catecholamine-induced endothelial dysfunction.