{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T18:51:45Z","timestamp":1771267905609,"version":"3.50.1"},"reference-count":37,"publisher":"Japan Atherosclerosis Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Atheroscler Thromb","JAT"],"published-print":{"date-parts":[[2018]]},"DOI":"10.5551\/jat.41335","type":"journal-article","created":{"date-parts":[[2017,10,31]],"date-time":"2017-10-31T22:13:01Z","timestamp":1509487981000},"page":"350-358","source":"Crossref","is-referenced-by-count":22,"title":["Alpha-2-macroglobulin as a Promising Biological Marker of Endothelial Function"],"prefix":"10.5551","volume":"25","author":[{"given":"Ryo","family":"Shimomura","sequence":"first","affiliation":[{"name":"Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohisa","family":"Nezu","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naohisa","family":"Hosomi","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiro","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takamichi","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoto","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mutsuko","family":"Araki","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayasu","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences"},{"name":"Hoshigaoka Medical Center, Japan Community Healthcare Organization (JCHO)"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3489","reference":[{"key":"1","unstructured":"1) LaMarre J, Wollenberg GK, Gauldie J, Hayes MA; Alpha 2-macroglobulin and serum preferentially counteract the mitoinhibitory effect of transforming growth factor-beta 2 in rat hepatocytes, Lab Invest, 1990; 62: 545-551"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Andus T, Gross V, Tran-Thi TA, Schreiber G, Nagashima M, Heinrich PC; The biosynthesis of acute-phase proteins in primary cultures of rat hepatocytes, Eur J Biochem, 1983; 133: 561-571","DOI":"10.1111\/j.1432-1033.1983.tb07500.x"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Hoogendoorn H, Toh CH, Nesheim ME, Giles Aet al; Alpha 2-macroglobulin binds and inhibits activated protein C, Blood, 1991; 78: 2283-2290","DOI":"10.1182\/blood.V78.9.2283.bloodjournal7892283"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Cvirn G, Gallistl S, Koestenberger M, Kutschera J, Leschnik B, Muntean W; Alpha 2-macroglobulin enhances prothrombin activation and thrombin potential by inhibiting the anticoagulant protein C\/protein S system in cord and adult plasma, Thromb Res, 2002; 105: 433-439","DOI":"10.1016\/S0049-3848(02)00042-7"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Cvirn G, Gallistl S, Muntean W; Effects of alpha(2)-macroglobulin and antithrombin on thrombin generation and inhibition in cord and adult plasma, Thromb Res, 2001; 101: 183-191","DOI":"10.1016\/S0049-3848(00)00389-3"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Matsuda T, Hirano T, Nagasawa S, Kishimoto T; Identification of alpha 2-macroglobulin as a carrier protein for IL-6, J Immunol, 1989; 142: 148-152","DOI":"10.4049\/jimmunol.142.1.148"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Rehman AA, Ahsan H, Khan FH; Alpha-2-macroglobulin: A physiological guardian, J Cell Physiol, 2013; 228: 1665-1675","DOI":"10.1002\/jcp.24266"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Nezu T, Hosomi N, Aoki S, Deguchi K, Masugata H, Ichihara N, Ohyama H, Ohtsuki T, Kohno M, Matsumoto M; Alpha2-macroglobulin as a promising biomarker for cerebral small vessel disease in acute ischemic stroke patients, J Neurol, 2013; 260: 2642-2649","DOI":"10.1007\/s00415-013-7040-x"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Pantoni L, Garcia JH; Pathogenesis of leukoaraiosis: a review, Stroke, 1997; 28: 652-659","DOI":"10.1161\/01.STR.28.3.652"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE; Noninvasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis, Lancet, 1992; 340: 1111-1115","DOI":"10.1016\/0140-6736(92)93147-F"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T; Circulating endothelial progenitor cells, vascular function, and cardiovascular risk, N Engl J Med, 2003; 348: 593-600","DOI":"10.1056\/NEJMoa022287"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Hosomi N, Aoki S, Matsuo K, Deguchi K, Masugata H, Murao K, Ichihara N, Ohyama H, Dobashi H, Nezu T, Ohtsuki T, Yasuda O, Soejima H, Ogawa H, Izumi Y, Kohno M, Tanaka J, Matsumoto M; Association of serum anti-periodontal pathogen antibody with ischemic stroke, Cerebrovasc Dis, 2012; 34: 385-392","DOI":"10.1159\/000343659"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A; Collaborators developing the Japanese equation for estimated GFR; Revised equations for estimated GFR from serum creatinine in Japan, Am J Kidney Dis, 2009; 53: 982-992","DOI":"10.1053\/j.ajkd.2008.12.034"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Nezu T, Hosomi N, Aoki S, Kubo S, Araki M, Mukai T, Takahashi T, Maruyama H, Higashi Y, Matsumoto M; Endothelial dysfunction is associated with the severity of cerebral small vessel disease, Hypertens Res, 2015; 38: 291-297","DOI":"10.1038\/hr.2015.4"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA; MR signal abnormalities at 1.5 T in Alzheimer&apos;s dementia and normal aging, AJR Am J Roentgenol, 1987; 149: 351-356","DOI":"10.2214\/ajr.149.2.351"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Duda DG, Cohen KS, Scadden DT, Jain RK; A protocol for phenotypic detection and enumeration of circulating endothelial cells and circulating progenitor cells in human blood, Nat Protoc, 2007; 2: 805-810","DOI":"10.1038\/nprot.2007.111"},{"key":"17","doi-asserted-by":"crossref","unstructured":"18) Ozdogu H, Sozer O, Boga C, Kozanoglu L, Maytalman E, Guzey M; Flow cytometric evaluation of circulating endothelial cells: a new protocol for identifying endothelial cells at several stages of differentiation, Am J Hematol, 2007; 82: 706-711","DOI":"10.1002\/ajh.20904"},{"key":"18","doi-asserted-by":"crossref","unstructured":"20) Dinarello CA; Reduction of inflammation by decreasing production of interleukin-1 or by specific receptor antagonism, Int J Tissue React, 1992; 14: 65-75","DOI":"10.1007\/978-3-642-76412-7_10"},{"key":"19","doi-asserted-by":"crossref","unstructured":"21) Horn F, Wegenka UM, L\u00fctticken C, Yuan J, Roeb E, Boers W, Buschmann J, Heinrich PC; Regulation of alpha 2-macroglobulin gene expression by interleukin-6, Ann N Y Acad Sci, 1994; 737: 308-323","DOI":"10.1111\/j.1749-6632.1994.tb44320.x"},{"key":"20","unstructured":"22) Ahmad J, Singh M, Saleemuddin M; A study of plasma alpha-2-macroglobulin levels in type 2 diabetic subjects with microalbuminuria, J Assoc Physicians India, 2001; 49: 1062-1065"},{"key":"21","unstructured":"23) Watzke H, Schernthaner G, Schnack C, Schwarz HP, Prskavec F, Freyler H; Coagulation factors of contact phase of haemostasis are normal in well-controlled type-I diabetic patients despite presence of diabetic retinopathy, Diabetes Res, 1988; 7: 197-200"},{"key":"22","doi-asserted-by":"crossref","unstructured":"24) Sottrup-Jensen L; Alpha-macroglobulins: structure, shape, and mechanism of proteinase complex formation, J Biol Chem, 1989; 264: 11539-11542","DOI":"10.1016\/S0021-9258(18)80094-1"},{"key":"23","doi-asserted-by":"crossref","unstructured":"25) Annapoorani P, Dhandapany PS, Sadayappan S, Ramasamy S, Rathinavel A, Selvam GS; Cardiac isoform of alpha-2 macroglobulin--a new biomarker for myocardial infarcted diabetic patients, Atherosclerosis, 2006; 186: 173-176","DOI":"10.1016\/j.atherosclerosis.2005.07.004"},{"key":"24","doi-asserted-by":"crossref","unstructured":"26) Rathinavel A, Dhandapany PS, Annapoorani P, Ramasamy S, Selvam GS; Cardiac isoform of alpha-2 macroglobulin as a novel diagnostic marker for cardiac diseases, Eur J Cardiovasc Prev Rehabil, 2005; 12: 601-603","DOI":"10.1097\/01.hjr.0000176513.07037.83"},{"key":"25","doi-asserted-by":"crossref","unstructured":"27) Rajamanickam C, Sakthivel S, Kurian Joseph P, Athimoolam Janarthanan R; A novel serum protein of molecular weight 182 kDa: a molecular marker for an early detection of increased left ventricular mass in patients with cardiac hypertrophy, J Cardiovasc Risk, 1998; 5: 335-338","DOI":"10.1097\/00043798-199810000-00009"},{"key":"26","doi-asserted-by":"crossref","unstructured":"28) Rosenzweig A; Circulating endothelial progenitors--cells as biomarkers, N Engl J Med, 2005; 353: 1055-1057","DOI":"10.1056\/NEJMe058134"},{"key":"27","doi-asserted-by":"crossref","unstructured":"29) Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, B\u00f6hm M, Nickenig G; Circulating endothelial progenitor cells and cardiovascular outcomes, N Engl J Med, 2005; 353: 999-1007","DOI":"10.1056\/NEJMoa043814"},{"key":"28","doi-asserted-by":"crossref","unstructured":"30) Idei N, Nishioka K, Soga J, Hidaka T, Hata T, Fujii Y, Fujimura N, Maruhashi T, Mikami S, Teragawa H, Kihara Y, Noma K, Chayama K, Higashi Y; Vascular function and circulating progenitor cells in thromboangitis obliterans (Buerger&apos;s disease) and atherosclerosis obliterans, Hypertension, 2011; 57: 70-78","DOI":"10.1161\/HYPERTENSIONAHA.110.163683"},{"key":"29","doi-asserted-by":"crossref","unstructured":"31) Donald AE, Halcox JP, Charakida M, Storry C, Wallace SM, Cole TJ, Friberg P, Deanfield JE; Methodological approaches to optimize reproducibility and power in clinical studies of flow-mediated dilation, J Am Coll Cardiol, 2008; 51: 1959-1964","DOI":"10.1016\/j.jacc.2008.02.044"},{"key":"30","doi-asserted-by":"crossref","unstructured":"32) Shahin Y, Khan JA, Samuel N, Chetter I; Angiotensin converting enzyme inhibitors effect on endothelial dysfunction: A meta-analysis of randomised controlled trials, Atherosclerosis, 2011; 216: 7-16","DOI":"10.1016\/j.atherosclerosis.2011.02.044"},{"key":"31","doi-asserted-by":"crossref","unstructured":"33) Perl S, Schm\u00f6lzer I, Sourij H, Pressl H, Eder M, Zweiker R, Wascher TC; Telmisartan improves vascular function independently of metabolic and antihypertensive effects in hypertensive subjects with impaired glucose tolerance, Int J Cardiol, 2010; 139: 289-296","DOI":"10.1016\/j.ijcard.2008.10.048"},{"key":"32","doi-asserted-by":"crossref","unstructured":"34) Economides PA, Caselli A, Tiani E, Khaodhiar L, Horton ES, Veves A; The effects of atorvastatin on endothelial function in diabetic patients and subjects at risk for type 2 diabetes, J Clin Endocrinol Metab, 2004; 89: 740-747","DOI":"10.1210\/jc.2003-031116"},{"key":"33","doi-asserted-by":"crossref","unstructured":"35) Kitagawa K, Hosomi N, Nagai Y, Kagimura T, Ohtsuki T, Origasa H, Minematsu K, Uchiyama S, Nakamura M, Matsumoto M; J-STARS Investigators. Reduction in highsensitivity c-reactive protein levels in patients with ischemic stroke by statin treatment: Hs-CRP sub-study in j-stars. J Atheroscler Thromb, 2017; 24: 1039-1047","DOI":"10.5551\/jat.39354"},{"key":"34","doi-asserted-by":"crossref","unstructured":"36) Oida K, Ebata K, Kanehara H, Suzuki J; Miyamori I, Effect of cilostazol on impaired vasodilatory response of the brachial artery to ischemia in smokers, J Atheroscler Thromb, 2003; 10: 93-98","DOI":"10.5551\/jat.10.93"},{"key":"35","doi-asserted-by":"crossref","unstructured":"37) Takase B, Nagata M, Hattori H, Tanaka Y, Ishihara M; Combined therapeutic effect of probucol and cilostazol on endothelial function in patients with silent cerebral lacunar infarcts and hypercholesterolemia: A preliminary study, Med Princ Pract, 2014; 23: 59-65","DOI":"10.1159\/000355825"},{"key":"36","doi-asserted-by":"crossref","unstructured":"38) Mori H, Maeda A, Wakabayashi K, Sato T, Sasai M, Tashiro K, Iso Y, Ebato M, Suzuki H; The effect of cilostazol on endothelial function as assessed by flow-mediated dilation in patients with coronary artery disease, J Atheroscler Thromb, 2016; 23: 1168-1177","DOI":"10.5551\/jat.32912"},{"key":"37","doi-asserted-by":"crossref","unstructured":"39) Ras RT, Streppel MT, Draijer R, Zock PL; Flow-mediated dilation and cardiovascular risk prediction: A systematic review with meta-analysis, Int J Cardiol, 2012; 168: 344-351","DOI":"10.1016\/j.ijcard.2012.09.047"}],"container-title":["Journal of Atherosclerosis and Thrombosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jat\/25\/4\/25_41335\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T20:31:11Z","timestamp":1750969871000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jat\/25\/4\/25_41335\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018]]}},"URL":"https:\/\/doi.org\/10.5551\/jat.41335","relation":{},"ISSN":["1340-3478","1880-3873"],"issn-type":[{"value":"1340-3478","type":"print"},{"value":"1880-3873","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018]]}}}