Biglycan expression, earlier vascular damage and pro-atherogenic profile improvement after smoke cessation in young people Giuseppe Mandraffino a, * , Caterina Oriana Aragona a , Michele Scuruchi b , Federica Mamone a , Angela D'Ascola b , Angela Alibrandi c , Maurizio Cinquegrani a , Carmela Morace a , Lilia Oreto d , Carlo Saitta a , Enricomaria Mormina e , Scipione Carerj d , Antonino Saitta a , Egidio Imbalzano a a Department of Clinical and Experimental Medicine, Internal Medicine Unit, University of Messina, Messina, Italy b Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy c Department of Statistics, University of Messina, Messina, Italy d Department of Clinical and Experimental Medicine, Cardiology Unit, University of Messina, Messina, Italy e Department of Biomedical Sciences and of Morphologic and Functional Images, University of Messina, Messina, Italy article info Article history: Received 28 July 2016 Received in revised form 12 December 2016 Accepted 12 January 2017 Available online 16 January 2017 Keywords: Arterial stiffness Vascular inflammation Atherosclerosis Proteoglycans Biglycan Smoking Smoke cessation abstract Background and aims: Young cigarette smokers may already present with early signs of vascular inflammation and damage; biglycan (BGN) has been shown to play a critical role in the initiation and progression of vascular lesions, also in young smokers. We investigated whether after smoke cessation, monocyte BGN expression is reduced; moreover, we evaluated any improvement of pro-atherogenic profile and arterial stiffness (AS), and their relationship with BGN in abstinent smokers. Methods: Two-hundred-fifty-one young people who had decided to quit smoking were enrolled; of these, 71 had completed the 12-month observation period maintaining smoking abstinence. At enroll- ment and 12 months later, we evaluated anthropometrics, laboratory profile, carotid-femoral pulse wave velocity (cf-PWV), carotid intima-media thickness (cIMT), BGN expression. Results: After 12-month smoke abstinence, we found a significant decrease in inflammatory markers (Hs-CRP: 23.3%; fibrinogen: 11.8%; IL-6: 9.2%), and increased HDL-C levels (þ9.3%); blood pressure values were also slightly reduced. cf-PWV (8.9%) appeared to be improved; cIMT remained unchanged. BGN expression appeared to be reduced (42.8% relative reduction). BGN reduction appeared to be associated with fibrinogen reduction, and smoking burden. Reduced cf-PWV appeared to be dependent on change in fibrinogen, SBP, IL-6, and BGN by multiple regression analysis. Conclusions: After the first year of smoke abstinence, the levels of IL-6, CRP, fibrinogen, HDL-C, and BGN expression, as well cf-PWV, are significantly improved as compared to baseline. This is the first evidence that removing exposure to a well-known cardiovascular risk factor, such as cigarette smoking, leads to significant reduction of BGN expression. © 2017 Elsevier B.V. All rights reserved. 1. Introduction Active cigarette smoking (CS) has been recently suggested to induce alterations in extracellular matrix (ECM) organization [1e4], also by enhancing the expression of the ECM organizer biglycan (BGN) [5]. BGN is a small leucine rich ECM stationary proteoglycan that organizes and maintains the architecture of ECM [6]. BGN is also released from ECM during tissue injury and after secretion from activated monocytes/macrophages, and in its soluble form may interact with several types of receptors, orchestrating their signaling [7,8] and influencing several biological processes, including modulation of growth factors, cytokines function and inflammatory response [9]. According to the “response-to-retention hypothesis” [10], and observations [11], BGN is recognized as a primary initiator of atherosclerosis due to its capability to trap lipoproteins in the * Corresponding author. Department of Clinical and Experimental Medicine, In- ternal Medicine Unit, University of Messina, v. Consolare Valeria e Gazzi, Messina, Italy. E-mail address: gmandraffino@unime.it (G. Mandraffino). Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis http://dx.doi.org/10.1016/j.atherosclerosis.2017.01.012 0021-9150/© 2017 Elsevier B.V. All rights reserved. Atherosclerosis 257 (2017) 109e115