Journal Article

Production of IL-8, VEGF and Elastase by Circulating and Intraplaque Neutrophils in Patients with Carotid Atherosclerosis

Tarallo, Antonino, Tozzi, Matteo, Scanzano, Angela, Ferraro, Stefania, Marino, Franca, Schembri, Laura, Castelli, Patrizio, Cosentino, Marco, Legnaro, Massimiliano

2015

Overview

Polymorphonuclear neutrophils (PMN) in atherosclerotic plaques have been identified only recently, and their contribution to plaque development is not yet fully understood. In this study, production of elastase, interleukin (IL)-8 and vascular endothelial growth factor (VEGF) by PMN was investigated in subjects with carotid stenosis undergoing carotid endarterectomy (CEA). The study enrolled 50 patients (Pts) and 10 healthy subjects (HS). Circulating PMN (cPMN) isolated from venous blood (in both Pts and HS) and from plaques (pPMN, in Pts) were cultured, alone or with 0.1 μM fMLP. Elastase, IL-8 and VEGF mRNA were analyzed by real-time PCR. In CEA specimens, PMN were localized by immunohistochemistry. In both Pts cPMN and pPMN, IL-8 mRNA was higher at rest but lower after fMLP (P<0.01 vs HS), and VEGF mRNA was higher both at rest and after fMLP (P<0.01 vs HS), while elastase mRNA was not significantly different. On the contrary, protein production was always higher in cPMN of HS with respect to values measured in cells of Pts. In CEA specimens, CD66b+ cells localized to areas with massive plaque formation close to neovessels. Pts with soft and mix plaques, as defined by computed tomography, did not differ in cPMN or pPMN IL-8, VEGF or elastase mRNA, or in intraplaque CD66b+ cell density. However, Pts with soft plaques had higher white blood cell count due to increased PMN. In Pts with carotid plaques, both circulating and intraplaque PMN produce IL-8, VEGF and elastase, which are crucial for plaque development and progression. These findings suggest mechanistic explanations to the reported correlation between PMN count and cardiovascular mortality in carotid ATH.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adults / Aged / Angina pectoris / Angiogenesis / Antigens, CD - metabolism / Arteriosclerosis / Atherosclerosis / Biology and life sciences / Blood / Blood circulation / Calcification / Cardiovascular disease / Cardiovascular diseases / Carotid arteries / Carotid Artery Diseases - genetics / Carotid Artery Diseases - metabolism / Carotid Artery Diseases - pathology / Cell Adhesion Molecules - metabolism / Cell density / Cell Movement / Cholesterol / Computed tomography / Elastase / Female / Formyl peptides / Gene Expression Regulation / Growth factors / Health aspects / Hospitals / Humans / Immunohistochemistry / Interleukin / Interleukin 8 / Interleukin-8 - biosynthesis / Interleukin-8 - genetics / Interleukins / Leukocytes / Leukocytes (neutrophilic) / Leukocytes (polymorphonuclear) / Male / Medicine and Health Sciences / Morphology / mRNA / Neutrophils / Neutrophils - metabolism / Pancreatic Elastase - biosynthesis / Pancreatic Elastase - genetics / Patients / Peptides / Pharmacology / Plaque, Atherosclerotic - metabolism / Plaques / Proteins / Real-Time Polymerase Chain Reaction / Research and analysis methods / RNA / Smooth muscle / Stenosis / Vascular endothelial growth factor / Vascular Endothelial Growth Factor A - biosynthesis / Vascular Endothelial Growth Factor A - genetics / Vascular surgery