Article Document Academic Article Information Content Entity Continuant Continuant Journal Article Entity Entity Generically Dependent Continuant 2025-06-26T12:46:48 RDF description of Adrenomedullin surges are linked to acute episodes of the systemic capillary leak syndrome (Clarkson disease) - http://repository.healthpartners.com/individual/document-rn7525 Journal of Leukocyte Biology 103 Adrenomedullin surges are linked to acute episodes of the systemic capillary leak syndrome (Clarkson disease) Blood 22846 2022-02-21T22:48:57.408-06:00 Cancer <p>BACKGROUND: Systemic Capillary Leak Syndrome (SCLS) is an extremely rare and life-threatening vascular disorder of unknown etiology. SCLS is characterized by abrupt and transient episodes of hypotensive shock and edema due to plasma leakage into peripheral tissues. The disorder has garnered attention recently because its initial presentation resembles more common vascular disorders including systemic anaphylaxis, sepsis, and acute infections with the Ebola/Marburg family of filoviruses. Although approximately 70-85% of patients with SCLS have a concurrent monoclonal gammopathy of unknown significance (MGUS), any contribution of the paraprotein to acute flares is unknown. PROCEDURE: To identify circulating factors that might trigger acute SCLS crises, we profiled transcriptomes of paired peripheral blood mononuclear cell fractions obtained from patients during acute attacks and convalescent intervals by microarray. RESULTS: This study uncovered 61 genes that were significantly up- or downregulated more than 2.5-fold in acute samples relative to respective baselines. One of the most upregulated genes was ADM, which encodes the vasoactive peptide adrenomedullin. A stable ADM protein surrogate (pro-ADM) was markedly elevated in SCLS acute sera compared to remission samples or sera from healthy controls. Monocytes and endothelial cells (ECs) from SCLS subjects expressed significantly more ADM in response to proinflammatory stimuli compared to healthy control cells. Application of ADM to ECs elicited protective effects on vascular barrier function, suggesting a feedback protective mechanism in SCLS. CONCLUSIONS: Since ADM has established hypotensive effects, differentiating between these dual actions of ADM is crucial for therapeutic applications aimed at more common diseases associated with increased ADM levels.<p> 4 Genetics document-rn7525 Cardiovascular Diseases 14133 public Case-Control Studies 10.1002/jlb.5a0817-324r