Signaling Components Involved in Leptin-Induced Amplification of the Atherosclerosis-Related Properties of Human Monocytes

• Published in: Journal of vascular research Vol. 46; no. 3; pp. 199 - 208
• Main Authors: Konstantinidis, Diamantis, Paletas, Konstantinos, Koliakos, George, Kaloyianni, Martha
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2009; S. Karger AG
• Subjects: Atherosclerosis (general aspects, experimental research); Atherosclerosis - etiology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cation Transport Proteins - physiology; CD36 Antigens - analysis; Cell Adhesion - drug effects; Cell Movement; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Humans; Laminin - physiology; Leptin - pharmacology; Lipoproteins, LDL - metabolism; Medical sciences; Monocytes - drug effects; Monocytes - physiology; NADPH Oxidases - physiology; Phosphatidylinositol 3-Kinases - physiology; Research Paper; Signal Transduction; Sodium-Hydrogen Exchanger 1; Sodium-Hydrogen Exchangers - physiology; Vertebrates: cardiovascular system; Monocytes; Leptin; Atherosclerosis; Cell adhesion; CD36; Cell migration; Oxidized low-density lipoproteins; Human; Monocyte; Cardiovascular disease; Adhesion; Vascular disease; Lipoprotein LDL; Cell motility; Signal transduction; Vertebrata; Mammalia; Circulatory system
• ISSN: 1018-1172; 1423-0135
• DOI: 10.1159/000161234

Background/Aims: Leptin, a 16-kDa cytokine that is released mainly by the adipose tissue, is known to affect a wide assortment of processes, ranging from energy homeostasis to angiogenesis and the immune response. In the present study, the effect of leptin on atherosclerosis-related properties of human monocytes was investigated. Methods: Monocytes were isolated from whole blood obtained from healthy donors who had normal body mass index values. Pharmacological inhibition of specific signaling proteins was implemented. Fluorescence spectrometry and immunofluorescence techniques, as well as ELISA methods, were utilized. Leptin dose response curves were determined for each type of experiment. Results: Leptin (160 ng/ml) was found to augment monocyte adhesion to laminin-1 and its migration through this glycoprotein, which is one of the main components of the extracellular matrix. Additionally, leptin increased CD36-receptor surface expression, as well as moderately oxidized low-density lipoprotein (oxLDL 3 ) uptake levels. Conclusion: Leptin amplifies the pro-atheromatic properties of human monocytes through a complex signaling net which involves the Na + /H + exchanger isoform-1, the actin cytoskeleton, phosphoinositide 3-kinase, certain conventional isoforms of protein kinase C and NADPH oxidase.