Advertisement

Endothelial glycocalyx and severity and vulnerability of coronary plaque in patients with coronary artery disease

      Highlights

      • Serum syndecan-1 level is not associated with angiographic coronary severity.
      • Lower syndecan-1 is associated with higher prevalence of vulnerable plaque.
      • Impairment of glycocalyx might be involved in the development of vulnerable plaque.

      Abstract

      Background and aims

      Endothelial glycocalyx covers the endothelium and maintains vascular integrity. However, its association with the severity and vulnerability of coronary artery disease (CAD) remains to be elucidated.

      Methods

      A total of 259 consecutive patients with stable CAD requiring percutaneous coronary intervention (PCI) were prospectively enrolled. Patients were classified into 2 groups according to the median value of serum syndecan-1, which is a core component of the endothelial glycocalyx (lower syndecan-1 group [syndecan-1 <99.0 ng/mL], n = 130; higher syndecan-1 group [syndecan-1 ≥99.0 ng/mL], n = 129). Severity of CAD and focal plaque vulnerability in culprit lesion were evaluated using angiography and optical coherence tomography.

      Results

      There was no significant difference in clinical characteristics between the lower syndecan-1 group and the higher syndecan-1 group other than the prevalence of family history of CAD (19 vs. 32%, p = 0.022), prior PCI history (45 vs. 60%, p = 0.015) and estimated glomerular filtration rate (57.8 ± 17.2 vs. 50.9 ± 25.6 ml/min/1.73 m2, p = 0.011). Although disease severity on angiogram was comparable between the 2 groups, the prevalence of lipid-rich plaque (40 vs. 19%, p = 0.004) and thin-cap fibroatheroma (20 vs. 6%, p = 0.006) was significantly higher in the lower syndecan-1 group than the higher syndecan-1 group. Lower syndecan-1 level was independently associated with higher prevalence of lipid-rich plaque (odds ratio 3.626, 95% confidence interval 1.535–8.566, p = 0.003).

      Conclusions

      Lower syndecan-1 level was associated with higher prevalence of vulnerable plaque in patients with CAD. This finding suggests the association between impaired endothelial glycocalyx and the development of vulnerable plaque.

      Graphical abstract

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Machin D.R.
        • Phuong T.T.
        • Donato A.J.
        The role of the endothelial glycocalyx in advanced age and cardiovascular disease.
        Curr. Opin. Pharmacol. 2019; 45: 66-71https://doi.org/10.1016/j.coph.2019.04.011
        • Nieuwdorp M.
        • Meuwese C.M.
        • Vink H.
        • Hoekstra J.B.
        • Kastelein J.J.
        • Stroes E.S.
        The endothelial glycocalyx: a potential barrier between health and vascular disease.
        Curr. Opin. Lipidol. 2005; 16: 507-511
        • Nieuwdorp M.
        • Mooij H.L.
        • Kroon J.
        • Atasever B.
        • Spaan J.A.E.
        • Ince C.
        • Holleman F.
        • Diamant M.
        • Heine R.J.
        • Hoekstra J.B.L.
        • Kastelein J.J.P.
        • Stroes E.S.G.
        • Vink H.
        Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes.
        Diabetes. 2006; 55: 1127-1132
        • Nieuwdorp M.
        • Van Haeften T.W.
        • Gouverneur M.C.L.G.
        • Mooij H.L.
        • Van Lieshout M.H.P.
        • Levi M.
        • Meijers J.C.M.
        • Holleman F.
        • Hoekstra J.B.L.
        • Vink H.
        • Kastelein J.J.P.
        • Stroes E.S.G.
        Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo.
        Diabetes. 2006; 55: 480-486
        • Broekhuizen L.N.
        • Lemkes B.A.
        • Mooij H.L.
        • Meuwese M.C.
        • Verberne H.
        Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus.
        Diabetologia. 2010; 53: 2646-2655https://doi.org/10.1007/s00125-010-1910-x
        • Padberg J.S.
        • Wiesinger A.
        • di Marco G.S.
        • Reuter S.
        • Grabner A.
        • Kentrup D.
        • Lukasz A.
        • Oberleithner H.
        • Pavenstädt H.
        • Brand M.
        • Kümpers P.
        Damage of the endothelial glycocalyx in chronic kidney disease.
        Atherosclerosis. 2014; 234: 335-343https://doi.org/10.1016/j.atherosclerosis.2014.03.016
        • Cancel L.M.
        • Ebong E.E.
        • Mensah S.
        • Hirschberg C.
        • Tarbell J.M.
        Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model Limary.
        Atherosclerosis. 2016; 252: 136-146https://doi.org/10.1016/j.physbeh.2017.03.040
        • Miranda C.H.
        • de Carvalho Borges M.
        • Schmidt A.
        • Marin-Neto J.A.
        • Pazin-Filho A.
        Evaluation of the endothelial glycocalyx damage in patients with acute coronary syndrome.
        Atherosclerosis. 2016; 247: 184-188https://doi.org/10.1016/j.atherosclerosis.2016.02.023
        • Nguyen T.H.
        • Liu S.
        • Ong G.J.
        • Stafford I.
        • Frenneaux M.P.
        • Horowitz J.D.
        Glycocalyx shedding is markedly increased during the acute phase of Takotsubo cardiomyopathy.
        Int. J. Cardiol. 2017; 243: 296-299https://doi.org/10.1016/j.ijcard.2017.04.085
        • Fujiyoshi K.
        • Minami Y.
        • Ishida K.
        • Kato A.
        • Katsura A.
        • Muramatsu Y.
        • Sato T.
        • Kakizaki R.
        • Nemoto T.
        • Hashimoto T.
        • Sato N.
        • Meguro K.
        • Shimohama T.
        • Tojo T.
        • Ako J.
        Incidence, factors, and clinical significance of cholesterol crystals in coronary plaque: an optical coherence tomography study.
        Atherosclerosis. 2019; 283: 79-84https://doi.org/10.1016/j.atherosclerosis.2019.02.009
        • Scalone G.
        • Niccoli G.
        • Refaat H.
        • Vergallo R.
        • Porto I.
        • Leone A.M.
        • Burzotta F.
        • D'Amario D.
        • Liuzzo G.
        • Fracassi F.
        • Trani C.
        • Crea F.
        Not all plaque ruptures are born equal: an optical coherence tomography study.
        Eur. Heart J. Cardiovasc. Imaging. 2017; 18: 1271-1277https://doi.org/10.1093/ehjci/jew208
        • Jang I.K.
        • Tearney G.J.
        • MacNeill B.
        • Takano M.
        • Moselewski F.
        • Iftima N.
        • Shishkov M.
        • Houser S.
        • Aretz H.T.
        • Halpern E.F.
        • others
        In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography.
        Circulation. 2005; 111: 1551-1555https://doi.org/10.1161/01.CIR.0000159354.43778.69
        • Tearney G.J.
        • Regar E.
        • Akasaka T.
        • Adriaenssens T.
        • Barlis P.
        • Bezerra H.G.
        • Bouma B.
        • Kume T.
        • Virmani R.
        • Weisz G.
        Consensus standards for acquisition , measurement , and reporting of intravascular optical coherence tomography studies A report from the international working group for intravascular optical coherence tomography standardization and validation.
        J. Am. Coll. Cardiol. 2012; 59: 1058-1072https://doi.org/10.1016/j.jacc.2011.09.079
        • Kitabata H.
        • Tanaka A.
        • Kubo T.
        • Takarada S.
        • Kashiwagi M.
        • Tsujioka H.
        • Ikejima H.
        • Kuroi A.
        • Kataiwa H.
        • Ishibashi K.
        • Komukai K.
        • Tanimoto T.
        • Ino Y.
        • Hirata K.
        • Nakamura N.
        • Mizukoshi M.
        • Imanishi T.
        • Akasaka T.
        Relation of microchannel structure identified by optical coherence tomography to plaque vulnerability in patients with coronary artery disease.
        Am. J. Cardiol. 2010; 105: 1673-1678https://doi.org/10.1016/j.amjcard.2010.01.346
        • Liu L.
        • Gardecki J.A.
        • Nadkarni S.K.
        • Toussaint J.D.
        • Yagi Y.
        • Bouma B.E.
        • Tearney G.J.
        Imaging the subcellular structure of human coronary atherosclerosis using 1-μm resolution optical coherence tomography (μOCT).
        Nat. Med. 2012; 17: 1010-1014https://doi.org/10.1038/nm.2409.Imaging
        • Ehara S.
        • Kobayashi Y.
        • Yoshiyama M.
        • Shimada K.
        • Shimada Y.
        • Fukuda D.
        • Nakamura Y.
        • Yamashita H.
        • Yamagishi H.
        • Takeuchi K.
        • Naruko T.
        • Haze K.
        • Becker A.E.
        • Yoshikawa J.
        • Ueda M.
        Spotty calcification typifies the culprit plaque in patients with acute myocardial infarction: an intravascular ultrasound study.
        Circulation. 2004; 110: 3424-3429https://doi.org/10.1161/01.CIR.0000148131.41425.E9
        • Ong D.S.
        • Lee J.S.
        • Soeda T.
        • Higuma T.
        • Minami Y.
        • Wang Z.
        • Lee H.
        • Yokoyama H.
        • Yokota T.
        • Okumura K.
        • Jang I.K.
        Coronary calcification and plaque vulnerability: an optical coherence tomographic study, Circ.
        Cardiovasc. Imaging. 2016; 9: 1-8https://doi.org/10.1161/CIRCIMAGING.115.003929
        • Steppan J.
        • Hofer S.
        • Funke B.
        • Brenner T.
        • Henrich M.
        • Ph D.
        • Martin E.
        • Hofmann U.
        • Weigand M.A.
        Sepsis and major abdominal surgery lead to flaking of the endothelial glycocalix sepsis causes marked increases in inflammatory markers.
        J. Surg. Res. 2011; 165: 136-141https://doi.org/10.1016/j.jss.2009.04.034
        • Rubio-gayosso I.
        • Platts S.H.
        • Duling B.R.
        • Platts S.H.
        • Duling B.R.
        Reactive oxygen species mediate modification of glycocalyx during ischemia-reperfusion injury.
        Am. J. Physiol. Heart Circ. Physiol. 2006; 290: 2247-2256https://doi.org/10.1152/ajpheart.00796.2005
        • Schmidt E.P.
        • Overdier K.H.
        • Sun X.
        • Lin L.
        • Liu X.
        • Yang Y.
        • Ammons L.A.
        • Hiller T.D.
        • Suflita M.A.
        • Yu Y.
        • Chen Y.
        • Zhang F.
        • Burlew C.C.
        • Edelstein C.L.
        • Douglas I.S.
        • Linhardt R.J.
        Urinary glycosaminoglycans predict outcomes in septic shock and acute respiratory distress syndrome.
        Am. J. Respir. Crit. Care Med. 2016; 194: 439-449https://doi.org/10.1164/rccm.201511-2281OC
        • Marechal X.
        • Favory R.
        • Joulin O.
        • Montaigne D.
        • Hassoun S.
        • Decoster B.
        • Zerimech F.
        • Neviere R.
        Endothelial glycocalyx damage during endotoxemia coincides with microcirculatory dysfunction and vascular oxidative stress.
        Shock. 2008; 29 (Endothelial): 572-576https://doi.org/10.1097/SHK.0b013e318157e926
        • Constantinescu A.A.
        • Vink H.
        • Spaan J.A.E.
        Elevated capillary tube hematocrit reflects degradation of endothelial cell glycocalyx by oxidized LDL.
        Am. J. Physiol. Heart Circ. Physiol. 2001; 280: 1051-1057https://doi.org/10.1152/ajpheart.2001.280.3.h1051
        • Mochizuki S.
        • Vink H.
        • Hiramatsu O.
        • Kajita T.
        • Shigeto F.
        • Spaan J.A.E.
        • Kajiya F.
        Role of hyaluronic acid glycosaminoglycans in shear-induced endothelium-derived nitric oxide release.
        Am. J. Physiol. Heart Circ. Physiol. 2003; 285: 722-726https://doi.org/10.1152/ajpheart.00691.2002
        • Rorije N.M.G.
        • Rademaker E.
        • Schrooten E.M.
        • Wouda R.D.
        • Homan Van Der Heide J.J.
        • Van Den Born B.J.H.
        • Vogt L.
        High-salt intake affects sublingual microcirculation and is linked to body weight change in healthy volunteers: a randomized cross-over trial.
        J. Hypertens. 2019; 37: 1254-1261https://doi.org/10.1097/HJH.0000000000002015
        • Van Den Berg B.M.
        • Spaan J.A.E.
        • Rolf T.M.
        • Vink H.
        Atherogenic region and diet diminish glycocalyx dimension and increase intima-to-media ratios at murine carotid artery bifurcation.
        Am. J. Physiol. Heart Circ. Physiol. 2006; 290: 915-920https://doi.org/10.1152/ajpheart.00051.2005
        • Vink H.
        • Constantinescu A.A.
        • Spaan J.A.
        Oxidized lipoproteins degrade the endothelial surface layer: implications for platelet-endothelial cell adhesion.
        Circulation. 2000; 101: 1500-1502https://doi.org/10.1161/01.CIR.0000108929.93074.0B