Annexin A1 in blood mononuclear cells from patients with coronary artery disease: Its association with inflammatory status and glucocorticoid sensitivity.
Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of glucocorticoid actions. In atherosclerotic tissue, increased expression of AnxA1 has been associated with protective plaque-stabilizing effects. Here, we investigated the expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Blood was collected from 57 patients with stable CAD (SCAD) and 41 healthy controls. We also included a minor group (n = 10) with acute coronary syndrome (ACS). AnxA1 mRNA was measured in PBMCs. Expression of AnxA1 protein (total and surface-bound) and glucocorticoid receptors (GR) were detected in PBMC subsets by flow cytometry. Also, salivary cortisol, interleukin(IL)-6 and IL-10 in plasma, and LPS-induced cytokine secretion from PBMCs, with or without dexamethasone, were assessed. AnxA1 mRNA was found to be slightly increased in PBMCs from SCAD patients compared with controls. However, protein expression of AnxA1 or GRs in PBMC subsets did not differ between SCAD patients and controls, despite SCAD patients showing a more proinflammatory cytokine profile ex vivo. Only surface expression of AnxA1 on monocytes correlated with dexamethasone-mediated suppression of cytokines. In ACS patients, a marked activation of AnxA1 was seen involving both gene expression and translocation of protein to cell surface probably reflecting a rapid glucocorticoid action modulating the acute inflammatory response in ACS. To conclude, surface expression of AnxA1 on monocytes may reflect the degree of glucocorticoid sensitivity. Speculatively, "normal" surface expression of AnxA1 indicates that anti-inflammatory capacity is impaired in SCAD patients.
Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.|Department of Clinical Immunology and Transfusion Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Ida
I
Bergström
Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Anna K
AK
Lundberg
Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Simon
S
Jönsson
Department of Clinical Medicine, School of Health and Medical Sciences, and iRiSC - Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Eva
E
Särndahl
Department of Clinical Immunology and Transfusion Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Jan
J
Ernerudh
Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Lena
http://orcid.org/0000-0002-0586-6618
L
Jonasson
D000368:Aged; D017305:Annexin A1 / Q000378:metabolism*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011965:Receptors, Glucocorticoid / Q000378:metabolism
D017305:Annexin A1; D016207:Cytokines; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone