Accumulation of Myeloperoxidase-Positive Neutrophils in Atherosclerotic Lesions in LDLR−/− Mice

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 28; no. 1; pp. 84 - 89
• Main Authors: van Leeuwen, Marcella, Gijbels, Marion J.J, Duijvestijn, Adriaan, Smook, Marjan, van de Gaar, Marie José, Heeringa, Peter, de Winther, Menno P.J, Tervaert, Jan Willem Cohen
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.01.2008; Hagerstown, MD Lippincott
• Subjects: Animals; Apolipoproteins E - genetics; Atherosclerosis (general aspects, experimental research); Atherosclerosis - immunology; Atherosclerosis - pathology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular system; Diet, Atherogenic; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Mice; Mice, Knockout; Neutrophils - metabolism; Neutrophils - pathology; Peroxidase - blood; Peroxidase - metabolism; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Receptors, LDL - genetics; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Immunohistochemistry; Enzyme; Rodentia; Cardiovascular disease; myeloperoxidase; Vascular disease; Vertebrata; Mammalia; Peroxidases; Mouse; Animal; Atherosclerosis; Peroxidase; Oxidoreductases; Neutrophil; LDLR-/- mice
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/ATVBAHA.107.154807

OBJECTIVE—Atherosclerosis is a chronic inflammatory disease in which the immune system plays an important role. Neutrophils have not been thoroughly studied in the context of atherogenesis. Here, we investigated neutrophils in the development of murine atherosclerotic lesions. METHODS AND RESULTS—LDLR mice were given a high-fat diet for different time periods and subsequently atherosclerotic lesions were studied by immunohistochemistry. Staining with anti–Ly-6G monoclonal antibody, a specific marker for neutrophils, revealed a marked accumulation of neutrophils during atherosclerosis development. Neutrophils were observed in the lesion, attached to the cap, and in the arterial adventitia. In addition, at some sites, neutrophil accumulation colocalized with endothelial E-selectin expression. Immunofluorescence double staining with anti-myeloperoxidase and anti–Ly-6G antibodies demonstrated the presence of myeloperoxidase in atherosclerotic lesions and its colocalization with neutrophils. After introducing the high-fat diet, levels of circulating myeloperoxidase in plasma strongly increased, with a peak at 6 weeks and a subsequent decrease to almost normal levels after 16 weeks of diet. CONCLUSIONS—We here demonstrate for the first time the presence of neutrophils and myeloperoxidase in murine atherosclerotic lesions. As a major cell type in inflammatory responses the neutrophil may also be an important mediator in the development of atherosclerosis.