Highlights
- •Biglycan (BGN) is a recognized early initiator of atherosclerosis and inflammation.
- •Young smokers without cardiovascular risk factors precociously present atherosclerosis.
- •BGN expression is increased in young smokers.
- •After 1 year of smoke cessation BGN decreases; HDL-C, inflammatory markers, and cf-PWV are significantly improved.
- •This observation may add a piece in the puzzle of the vascular damaging induced by cigarette smoking.
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 enrollment 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 (+9.3%);
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.
Keywords
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References
- Cigarette smoke enhances proliferation and extracellular matrix deposition by human fetal airway smooth muscle.Am. J. Physiol. Lung Cell Mol. Physiol. 2014; 307: L978-L986
- Remodeling of aorta extracellular matrix as a result of transient high oxygen exposure in newborn rats: implication for arterial rigidity and hypertension risk.PLoS One. 2014; 9: e92287
- Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells.Biochem. J. 2014; 459: 313-322
- Vascular wall extracellular matrix proteins and vascular diseases.Biochim. Biophys. Acta. 2014; 1842: 2106-2119
- Biglycan expression in current cigarette smokers: a possible link between active smoking and atherogenesis.Atherosclerosis. 2014; 237: 471-479
- Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis.FASEB J. 2002; 16: 673-680
- Biglycan: a multivalent proteoglycan providing structure and signals.J. Histochem Cytochem. 2012; 60: 963-975
- Biological interplay between proteoglycans and their innate immune receptors in inflammation.FEBS J. 2013; 280: 2165-2179
- Biglycan, a danger signal that activates the NLRP3 inflammasome via toll-like and P2X receptors.J. Biol. Chem. 2009; 284: 24035-24048
- The response-to-retention hypothesis of atherogenesis reinforced.Curr. Opin. Lipidol. 1998; 9: 471-474
- Smooth muscle cell biglycan overexpression results in increased lipoprotein retention on extracellular matrix: implications for the retention of lipoproteins in atherosclerosis.Atherosclerosis. 2004; 177: 29-35
- Aggregation and fusion of low-density lipoproteins in vivo and in vitro.Biomol. Concepts. 2013; 4: 501-518
- The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages.J. Clin. Invest. 2005; 115: 2223-2233
- Biglycan: unpuzzling the causal links between tobacco-smoking and atherosclerosis?.Atherosclerosis. 2014; 237: 809-810
- Nicotine induces mitogen-activated protein kinase dependent vascular smooth muscle cell migration.Atherosclerosis. 2005; 178: 271-277
- Smoke exposure and circulating progenitor cells: evidence for modulation of antioxidant enzymes and cell count.Clin. Biochem. 2010; 43: 1436-1442
- Effects of smoking on arterial distensibility, central aortic pressures and left ventricular mass.Int. J. Cardiol. 2013; 168: 2593-2601
- Oxidative stress and accelerated vascular aging: implications for cigarette smoking.Front. Biosci. Landmark Ed. 2009; 14: 3128-3144
- Associations between cigarette smoking, pipe/cigar smoking, and smoking cessation, and haemostatic and inflammatory markers for cardiovascular disease.Eur. Heart J. 2005; 26: 1765-1773
- Decorin and biglycan retain LDL in disease-prone valvular and aortic subendothelial intimal matrix.Atherosclerosis. 2014; 233: 113-121
- The pathophysiology of cigarette smoking and cardiovascular disease: an update.J. Am. Coll. Cardiol. 2004; 43: 1731-1737
- The biology behind the atherothrombotic effects of cigarette smoke.Nat. Rev. Cardiol. 2013; 10: 219-230
- Cigarette smoking and inflammation revisited.Respir. Physiol. Neurobiol. 2013; 187: 5-10
- Smoking cessation and cardiovascular disease risk factors: results from the third national health and nutrition examination survey.PLoS Med. 2005; 2: e160
- Non smoking for successful aging: therapeutic perspectives.Curr. Pharm. Des. 2010; 16: 775-782
- Smoking and all-cause mortality in older people: systematic review and meta-analysis.Arch. Intern Med. 2012; 172: 837-844
- Mortality in relation to smoking: 50 years' observations on male British doctors.BMJ. 2004; 328: 1519
- Smoking cessation.Chest. 2010; 137: 428-435
- Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis.Arterioscler. Thromb. Vasc. Biol. 2014; 34: 509-515
- Pulse wave velocity and augmentation index, but not intima-media thickness, are early indicators of vascular damage in hypercholesterolemic children.Eur. J. Clin. Invest. 2010; 40: 250-257
- Biglycan expression in hypertensive subjects with normal or increased carotid intima-media wall thickness.Clin. Chim. Acta. 2009; 406: 89-93
- ESH-ESC practice guidelines for the management of arterial hypertension: ESH-ESC task force on the management of arterial hypertension.J. Hypertens. 2007; 25: 1751-1762
- Atherogenesis in youth–early consequence of adolescent smoking.Atherosclerosis. 2013; 230: 304-309
- Nicotine induces the expression of C-reactive protein via MAPK-dependent signal pathway in U937 macrophages.Mol. Cells. 2012; 34: 457-461
- Cigarette smoking influences cytokine production and antioxidant defences.Clin. Sci. (Lond). 1995; 88: 485-489
- Inflammation and atherosclerosis: direct versus indirect mechanisms.Curr. Opin. Pharmacol. 2013; 13: 154-160
- High-density lipoproteins in the prevention of cardiovascular disease: changing the paradigm.Clin. Pharmacol. Ther. 2014; 96: 48-56
- Smoking and smoking cessation – the relationship between cardiovascular disease and lipoprotein metabolism: a review.Atherosclerosis. 2008; 201: 225-235
- The effect of quitting smoking on HDL-cholesterol - a review based on within-subject changes.Biomark. Res. 2013; 1: 26
- Impact of smoking cessation and lifetime exposure on C-reactive protein.Nicotine Tob. Res. 2008; 10: 637-642
- Plasma suPAR is lowered by smoking cessation: a randomized controlled study.Eur. J. Clin. Investigation. 2016; 46: 305-311
- A pilot study to examine the effects of smoking cessation on serum markers of inflammation in women at risk for cardiovascular disease.Chest. 2009; 136: 212-219
- Persistence of smoking-induced dysregulation of MiRNA expression in the small airway epithelium despite smoking cessation.PLoS One. 2015; 10: e0120824
- Arterial stiffness: a brief review.Acta Pharmacol. Sin. 2010; 31: 1267-1276
- Impact of smoking and smoking cessation on arterial stiffness and aortic wave reflection in hypertension.Hypertension. 2007; 49: 981-985
- Functional relevance of protein glycosylation to the pro-inflammatory effects of extracellular matrix metalloproteinase inducer (EMMPRIN) on monocytes/macrophages.PLoS One. 2015; 10: e0117463
- Nicotine exposure alters human vascular smooth muscle cell phenotype from a contractile to a synthetic type.Atherosclerosis. 2014; 237: 464-470
- Hyperelongated biglycan: the surreptitious initiator of atherosclerosis.Curr. Opin. Lipidol. 2008; 19: 448-454
- Small leucine-rich proteoglycans orchestrate receptor crosstalk during inflammation.Cell Cycle. 2012; 11: 2084-2091
- Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data.BMJ. 1989; 298: 784-788
- Low density lipoprotein particle size and coronary artery disease.Arterioscler. Thromb. 1992; 12: 187-195
- Smoking and small, dense low-density lipoprotein particles: cross-sectional study.Nicotine Tob. Res. 2008; 10: 1391-1395
- Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractions: relative contribution of small, dense LDL to coronary heart disease risk.Atherosclerosis. 1994; 106: 241-253
- Smoking status is inversely associated with overall diet quality: findings from the ORISCAV-LUX study.Clin. Nutr. 2016 Aug 24; (pii: S0261-5614(16)30212-6)https://doi.org/10.1016/j.clnu.2016.08.013
- Association of smoking status, insulin resistance, body mass index, and metabolic syndrome in workers: a 1-year follow-up study.Obes. Res. Clin. Pract. 2010; 4: e163-246
- Association of smoking status, weight change, and incident metabolic syndrome in men: a 3-year follow-up study.Diabetes Care. 2009; 32: 1314-1316
- Regulation of ICAM-1 (CD54) expression in human breast cancer cell lines by interleukin 6 and fibroblast-derived factors.Int. J. Cancer. 1994; 58: 80-84
- Transcriptional regulation of the human biglycan gene.J. Biol. Chem. 1996; 271: 15787-15795
- Effects of the angiotensin II receptor blocker losartan on the monocyte expression of biglycan in hypertensive patients.Clin. Exp. Pharmacol. Physiol. 2010; 37: 933-938
- Novel extracellular matrix biomarkers as predictors of adverse outcome in chronic heart failure: association between biglycan and response to statin therapy in the CORONA trial.J. Card. Fail. 2015; 21: 153-159
Article info
Publication history
Published online: January 14, 2017
Accepted:
January 12,
2017
Received in revised form:
December 12,
2016
Received:
July 28,
2016
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.