title: Biglycan expression in current cigarette smokers: a possible link between active smoking and atherogenesis.
abstract: OBJECTIVE
  Cigarette smokers present early signs of vascular damage and systemic inflammation. Biglycan (BGN), an ubiquitous component of extracellular matrix orchestrating several physiological functions, has recently been indicated as a major source of low-density lipoprotein retention in the normal arterial intima-media layer. We evaluated whether BGN-mRNA expression was enhanced in peripheral monocytes of smokers with no additional cardiovascular risk factors (CVRFs), and if it was associated with altered carotid arterial stiffness (AS) or intima media thickness (cIMT). We also evaluated plasma markers of systemic and vascular inflammation, and correlation with BGN-mRNA.
  
  
  METHODS
  Two-hundred-fifty-one young smokers were enrolled, with no additional CVRFs, and 60 controls. Plasma lipids, fibrinogen, C-reactive protein (CRP), interleukin-6 (IL-6), AS and cIMT were assessed. A smoke exposure index (SEIx) was calculated.
  
  
  RESULTS
  Fibrinogen, CRP, AS indices, cIMT, and BGN-mRNA were higher in smokers compared to controls; HDL-C levels were lower, no difference was detected in IL-6 levels. After stratification of smokers in quartiles based on SEIx values, smokers in the highest quartiles presented highest fibrinogen, CRP, AS, cIMT, BGN, and also IL-6 values, and lowest HDL-C.
  
  
  CONCLUSIONS
  BGN-mRNA was enhanced in young smokers, compared to controls, and appears associated to a proatherogenic profile, characterized by increased fibrinogen, CRP, and IL-6, lower HDL-C, altered AS and cIMT values, particularly in those with higher SEIx: the more cigarettes smoked over years, the more marked the alterations. Although we cannot state whether BGN have a direct causal role in inducing, maintaining and developing vascular damage, including intima-media wall thickening and arterial stiffening, our data could suggest that it may represent a link between proatherogenic status induced by cigarette smoking, and the development and progression of vascular damage.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy. Electronic address: gmandraffinomd@libero.it.
authors.forename: G
authors.initials: G
authors.lastname: Mandraffino
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Imbalzano
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Mamone
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: C O
authors.initials: CO
authors.lastname: Aragona
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lo Gullo
authors.affiliation: Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: D'Ascola
authors.affiliation: Department of Statistics, University of Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Alibrandi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cinquegrani
authors.affiliation: Department of Biomedical Sciences and of Morphologic and Functional Images, University of Messina, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Mormina
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Versace
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Basile
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Sardo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cinquegrani
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Carerj
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Saitta
mesh_terms: D000293:Adolescent; D000328:Adult; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology*; D058578:Biglycan / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D002339:Carotid Arteries / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D002784:Cholesterol / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012044:Regression Analysis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D055815:Young Adult
chemical_list: C546884:BGN protein, human; D058578:Biglycan; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D012313:RNA; D002097:C-Reactive Protein; D002784:Cholesterol
keywords: Biglycan; Cigarette smoking; Monocytes; Smoke exposure; Vascular damage; Vascular inflammation