Endothelial damage in major depression patients is modulated by SSRI treatment, as demonstrated by circulating biomarkers and an in vitro cell model.
There is a link between depression, cardiovascular events and inflammation. We have explored this connection through endothelial dysfunction, using in vivo and in vitro approaches. We evaluated circulating biomarkers of endothelial dysfunction in patients with major depression at their diagnosis (MD-0) and during antidepressant treatment with the selective serotonin reuptake inhibitor escitalopram, for 8 and 24 weeks (MD-8 and MD-24). Results were always compared with matched healthy controls (CON). We measured in vivo circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) in blood samples, and assessed plasma levels of soluble von Willebrand factor (VWF) and vascular cell adhesion molecule-1 (VCAM-1). CEC counts, soluble VWF and VCAM-1 were statistically elevated in MD-0 (P<0.01 versus CON) and gradually decreased during treatment. Conversely, EPC levels were lower in MD-0, tending to increase throughout treatment. In vitro studies were performed in human endothelial cells cultured in the presence of sera from each study group. Elevated expression of the inflammation marker intercellular adhesion molecule-1 and oxidative stress, with lower presence of endothelial nitric oxide synthase and higher reactive oxygen species production, were found in cells exposed to MD-0 sera (P<0.05 versus CON). These results were normalized in cells exposed to MD-24 sera. Thrombogenicity of extracellular matrices generated by these cells, measured as expression of VWF, tissue factor and platelet reactivity, showed non-significant differences. We provide a model of cultured endothelial cells reproducing endothelial dysfunction in naive patients with major depression, demonstrating endothelial damage and inflammation at diagnosis, and recovering with selective serotonin reuptake inhibitor treatment for 24 weeks.
Department of Hemotherapy and Hemostasis, Hospital Clinic of Barcelona, Biomedical Diagnosis Centre, Institute of Biomedical Research August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
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Lopez-Vilchez
Department of Hemotherapy and Hemostasis, Hospital Clinic of Barcelona, Biomedical Diagnosis Centre, Institute of Biomedical Research August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
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Diaz-Ricart
Department of Psychiatry, Hospital Clinic of Barcelona, Institute Clinic of Neurosciences, Barcelona, Spain.
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Navarro
Department of Hemotherapy and Hemostasis, Hospital Clinic of Barcelona, Biomedical Diagnosis Centre, Institute of Biomedical Research August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
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Torramade
Department of Medicine, School of Medicine, Complutense University, Madrid, Spain.
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Zamorano-Leon
Department of Medicine, School of Medicine, Complutense University, Madrid, Spain.
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Lopez-Farre
Department of Hemotherapy and Hemostasis, Hospital Clinic of Barcelona, Biomedical Diagnosis Centre, Institute of Biomedical Research August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
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Galan
Department of Psychiatry, Hospital Clinic of Barcelona, Institute Clinic of Neurosciences, Barcelona, Spain.
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Gasto
Department of Hemotherapy and Hemostasis, Hospital Clinic of Barcelona, Biomedical Diagnosis Centre, Institute of Biomedical Research August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
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Escolar
D000328:Adult; D016022:Case-Control Studies; D015283:Citalopram / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D066026:Endothelial Progenitor Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005109:Extracellular Matrix; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D015539:Platelet Activation; D017382:Reactive Oxygen Species / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism*
D015283:Citalopram; D052250:Nitric Oxide Synthase Type III; D017382:Reactive Oxygen Species; D017367:Selective Serotonin Reuptake Inhibitors; D013925:Thromboplastin; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; C496314:NOS3 protein, human