Advertisement

Soluble LR11 is a novel biomarker for vascular lesions late after Kawasaki disease

      Highlights

      • Soluble LR11 (sLR11) is a novel biomarker for vascular lesions.
      • sLR11 levels in Kawasaki disease patients with coronary artery lesions are high.
      • Serum sLR11 could be a biomarker for vascular lesions late after Kawasaki disease.

      Abstract

      Objective

      Coronary artery lesions (CALs) and a risk for early onset of atherosclerosis are major concerns following Kawasaki disease (KD). Intimal smooth muscle cells (SMCs) have an important role in vascular lesions in KD. It is known that soluble LR11 (sLR11) is a novel biomarker for vascular lesions and LR11 is markedly expressed in intimal SMCs in atherosclerotic lesions. In this study, we hypothesized that sLR11 reflects the presence of vascular lesions late after KD.

      Methods

      Twenty-three age-matched controls (group 1) and 59 patients with a history of KD were enrolled; 36 with KD had normal coronary arteries or regressed aneurysms (group 2), and 23 had CALs (group 3).

      Results

      Serum sLR11 levels in group 3 (median, interquartile range (IQR): 11.1 ng/mL, 9.3–13.9 ng/mL) were significantly higher than those in groups 1 (8.4 ng/mL, 7.1–10.2 ng/mL, p < 0.001) and 2 (9.0 ng/mL, 7.7–10.1 ng/mL, p < 0.01). Levels of sLR11 were positively correlated with levels of high-sensitivity C-reactive protein (r = 0.480, p < 0.01) and lipoprotein (a) (r = 0.486, p < 0.01).

      Conclusion

      These findings suggest that sLR11 reflects the development of vascular lesions in patients with serious CALs.

      Keywords

      Abbreviations:

      CAL (coronary artery lesion), KD (kawasaki disease), hs-CRP (high-sensitivity C-reactive protein), SMCs (smooth muscle cells)
      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

        • Kawasaki T.
        Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children.
        Arerugi. 1967; 16: 178-222
        • Suzuki A.
        • Kamiya T.
        • Kuwahara N.
        • et al.
        Coronary arterial lesions of Kawasaki disease: cardiac catheterization findings of 1100 cases.
        Pediatr. Cardiol. 1986; 7: 3-9
        • Kato H.
        • Sugimura T.
        • Akagi T.
        • et al.
        Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients.
        Circulation. 1996; 94: 1379-1385
        • Zhu Y.
        • Bujo H.
        • Yamazaki H.
        • et al.
        LR11, an LDL receptor gene family member, is a novel regulator of smooth muscle cell migration.
        Circ. Res. 2004; 94: 752-758
        • Zhu Y.
        • Bujo H.
        • Yamazaki H.
        • et al.
        Enhanced expression of the LDL receptor family member LR11 increases migration of smooth muscle cells in vitro.
        Circulation. 2002; 105: 1830-1836
        • Kanaki T.
        • Bujo H.
        • Hirayama S.
        • et al.
        Expression of LR11, a mosaic LDL receptor family member, is markedly increased in atherosclerotic lesions.
        Arterioscler. Thromb. Vasc. Biol. 1999; 19: 2687-2695
        • Takahashi M.
        • Bujo H.
        • Jiang M.
        • Noike H.
        • Saito Y.
        • Shirai K.
        Enhanced circulating soluble LR11 in patients with coronary organic stenosis.
        Atherosclerosis. 2010; 210: 581-584
        • Jiang M.
        • Bujo H.
        • Ohwaki K.
        • et al.
        Ang II-stimulated migration of vascular smooth muscle cells is dependent on LR11 in mice.
        J. Clin. Invest. 2008; 118: 2733-2746
        • Ogita M.
        • Miyauchi K.
        • Dohi T.
        • et al.
        Increased circulating soluble LR11 in patients with acute coronary syndrome.
        Clin. Chim. Acta. 2013; 415: 191-194
      1. Disease. RCoK. Report of subcommittee on standardization of diagnostic criteria and reporting of coronary artery lesions in Kawasaki disease. 1984.

        • Matsuo M.
        • Ebinuma H.
        • Fukamachi I.
        • Jiang M.
        • Bujo H.
        • Saito Y.
        Development of an immunoassay for the quantification of soluble LR11, a circulating marker of atherosclerosis.
        Clin. Chem. 2009; 55: 1801-1808
        • Takahashi M.
        • Mason W.
        • Lewis A.B.
        Regression of coronary aneurysms in patients with Kawasaki syndrome.
        Circulation. 1987; 75: 387-394
        • Sasaguri Y.
        • Kato H.
        Regression of aneurysms in Kawasaki disease: a pathological study.
        J. Pediatr. 1982; 100: 225-231
        • Sugimura T.
        • Kato H.
        • Inoue O.
        • et al.
        Intravascular ultrasound of coronary arteries in children. Assessment of the wall morphology and the lumen after Kawasaki disease.
        Circulation. 1994; 89: 258-265
        • Suzuki A.
        • Miyagawa-Tomita S.
        • Komatsu K.
        • et al.
        Active remodeling of the coronary arterial lesions in the late phase of Kawasaki disease: immunohistochemical study.
        Circulation. 2000; 101: 2935-2941
        • Suzuki A.
        • Miyagawa-Tomita S.
        • Komatsu K.
        • et al.
        Immunohistochemical study of apparently intact coronary artery in a child after Kawasaki disease.
        Pediatr. Int. 2004; 46: 590-596
        • Dhillon R.
        • Clarkson P.
        • Donald A.E.
        • et al.
        Endothelial dysfunction late after Kawasaki disease.
        Circulation. 1996; 94: 2103-2106
        • Kadono T.
        • Sugiyama H.
        • Hoshiai M.
        • et al.
        Endothelial function evaluated by flow-mediated dilatation in pediatric vascular disease.
        Pediatr. Cardiol. 2005; 26: 385-390
        • Ridker P.M.
        • Danielson E.
        • Fonseca F.A.
        • et al.
        Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.
        N. Engl. J. Med. 2008; 359: 2195-2207
        • Baigent C.
        • Blackwell L.
        • Emberson J.
        • et al.
        Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.
        Lancet. 2010; 376: 1670-1681
        • Okazaki S.
        • Yokoyama T.
        • Miyauchi K.
        • et al.
        Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the establish Study.
        Circulation. 2004; 110: 1061-1068
        • Jiang M.
        • Bujo H.
        • Zhu Y.
        • et al.
        Pitavastatin attenuates the PDGF-induced LR11/uPA receptor-mediated migration of smooth muscle cells.
        Biochem. Biophys. Res. Commun. 2006; 348: 1367-1377
        • Bujo H.
        • Saito Y.
        Modulation of smooth muscle cell migration by members of the low-density lipoprotein receptor family.
        Arterioscler. Thromb. Vasc. Biol. 2006; 26: 1246-1252
        • Hamaoka A.
        • Hamaoka K.
        • Yahata T.
        • et al.
        Effects of HMG-CoA reductase inhibitors on continuous post-inflammatory vascular remodeling late after Kawasaki disease.
        J. Cardiol. 2010; 56: 245-253
        • Huang S.M.
        • Weng K.P.
        • Chang J.S.
        • Lee W.Y.
        • Huang S.H.
        • Hsieh K.S.
        Effects of statin therapy in children complicated with coronary arterial abnormality late after Kawasaki disease: a pilot study.
        Circ. J. 2008; 72: 1583-1587