Increased YKL-40 expression in patients with carotid atherosclerosis

• Published in: Atherosclerosis Vol. 211; no. 2; pp. 589 - 595
• Main Authors: Michelsen, Annika E, Rathcke, Camilla N, Skjelland, Mona, Holm, Sverre, Ranheim, Trine, Krohg-Sørensen, Kirsten, Klingvall, Marit F, Brosstad, Frank, Øie, Erik, Vestergaard, Henrik, Aukrust, Pål, Halvorsen, Bente
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.08.2010; Elsevier
• Subjects: Adipokines; Adult; Aged; Aged, 80 and over; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; Carotid artery; Carotid Artery Diseases - blood; Case-Control Studies; Chitinase-3-Like Protein 1; Female; Gene Expression Regulation; Glycoproteins - biosynthesis; Humans; Inflammation; Lectins - biosynthesis; Macrophage; Macrophage Activation; Macrophages - metabolism; Male; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Middle Aged; Monocytes - cytology; Neovascularization, Pathologic; Neurosurgery; p38 Mitogen-Activated Protein Kinases - metabolism; Platelet releasate; Skull, brain, vascular surgery; Stroke; Stroke - pathology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Ventricular Remodeling; Stroke; Inflammation; Carotid artery; Platelet releasate; Atherosclerosis; Macrophage; Human; Nervous system diseases; Cardiovascular disease; Artery; Cerebral disorder; Vascular disease; Platelet; Blood vessel; Carotid; Central nervous system disease; Circulatory system; Cerebrovascular disease
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2010.02.035

Abstract Objective We hypothesized a role for the inflammatory protein YKL-40 in atherogenesis and plaque destabilization based on its role in macrophage activation, tissue remodeling, and angiogenesis. Methods Serum YKL-40 levels were measured by enzyme immunoassay in 89 patients with carotid atherosclerosis and 20 healthy controls. Carotid expression of YKL-40 was examined by real time RT-PCR in 57 of the patients. Regulation and effect of YKL-40 were examined in THP-1 monocytes. Results Our main findings were: (1) serum YKL-40 levels were significantly elevated in patients with carotid atherosclerosis, with particularly high levels in those with symptomatic disease; (2) patients with recent ischemic symptoms (within 2 months) had higher YKL-40 mRNA levels in carotid plaque than other patients; (3) in vitro , the β-adrenergic receptor agonist isoproterenol, toll-like receptor (TLR) 2 and TLR4 agonists, and in particular releasate from activated platelets significantly increased the expression of YKL-40 in THP-1 monocytes and (4) in vitro , YKL-40 increased matrix metalloproteinase-9 expression and activity in THP-1 monocytes, involving activation of p38 mitogen-activated protein kinase. Conclusions Our findings suggest that YKL-40 might be a marker of plaque instability, potentially reflecting macrophage activation and matrix degradation within the atherosclerotic lesion.