Decreased fibrocyte number is associated with atherosclerotic plaque instability in man

Abstract

Aims Plaque rupture partly results from inadequate collagen synthesis due to lower smooth muscle cell numbers in fibrous caps. Fibrocytes are bone-marrow-derived circulating mesenchymal progenitors and have recently been identified in fibrous caps. This study hypothesized that reduced fibrocyte numbers would be associated with plaque instability. Methods and results Patients with acute myocardial infarction (MI) (n = 22), stable angina (SA) (n = 20), or healthy controls (n = 22) were recruited. Circulating fibrocytes (CD45 +/CD34 +/collagen I +) were measured by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were isolated from blood and cultured for 2 weeks, and fibrocytes were quantified by morphology (spindle-shaped) and flow cytometry (CD45 +/collagen I +). Another set of PBMCs was stimulated with macrophage colony-stimulating factor (M-CSF) for 72 h and the expression of several macrophage markers was measured by flow cytometry. Acute MI patients had decreased circulating fibrocyte numbers compared with healthy controls or SA patients. Following 2 weeks culture, both the number of spindle-shaped fibrocytes counted under the microscope and the percentage of fibrocytes of the remaining adherent cells in culture measured by flow cytometry were reduced in acute MI patients. Expression of macrophage markers CD68, CD36, and EMR in M-CSF-stimulated PBMCs was enhanced in acute MI patients compared with the other two groups. SA patients with previous MI had decreased circulating fibrocyte numbers and a lower yield of fibrocytes from PBMCs than those without previous MI. Conclusion sThis is the first report of decreased fibrocyte numbers in patients with MI. Reduced fibrocytes and preferential differentiation of PBMCs into macrophages may contribute to plaque instability. Published on behalf of the European Society of Cardiology. All rights reserved. © 2012 The Author.