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Serotonin in peripheral blood reflects oxidative stress and plays a crucial role in atherosclerosis: Novel insights toward holistic anti-atherothrombotic strategy

      Abstract

      We enrolled 132 outpatients with cardiovascular risk factors to evaluate the serotonin levels in platelet-poor plasma (PPP) and whole blood (WB). PPP serotonin levels and PPP/WB serotonin ratio were significantly correlated with levels of oxidative stress measured by derivative reactive oxygen metabolites (d-ROM). Twenty-five subjects were revealed to have stable coronary artery disease (CAD), and the levels CRP, d-ROM, and PPP/WB serotonin ratio were significantly higher in subjects with CAD than in those without CAD. Logistic regression analysis performed with the endpoint of having CAD revealed that the PPP/WB serotonin ratio was independently associated with CAD (odds ratio 3.37, 95% confidence interval 1.04–10.9, P = 0.04). Receiver operating characteristic (ROC) curve analyses to discriminate subjects with CAD from those without CAD indicated that combining PPP/WB serotonin ratio and d-ROM improved diagnostic utility. Targeting the serotonin–oxidative stress axis as part of a holistic anti-atherothrombotic strategy could be beneficial for patients with atherosclerosis.

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      References

        • Vanhoutte P.M.
        Endothelial dysfunction and vascular disease.
        Verh. K. Acad. Geneeskd. Belg. 1998; 60: 251-266
        • Hara K.
        • Hirowatari Y.
        • Yoshika M.
        • Komiyama Y.
        • Tsuka Y.
        • Takahashi H.
        The ratio of plasma to whole-blood serotonin may be a novel marker of atherosclerotic cardiovascular disease.
        J. Lab. Clin. Med. 2004; 144: 31-37
        • Figueras J.
        • Domingo E.
        • Cortadellas J.
        • Padilla F.
        • Dorado D.G.
        • Segura R.
        • et al.
        Comparison of plasma serotonin levels in patients with variant angina pectoris versus healed myocardial infarction.
        Am. J. Cardiol. 2005; 96: 204-207
        • Vikenes K.
        • Farstad M.
        • Nordrehaug J.E.
        Serotonin is associated with coronary artery disease and cardiac events.
        Circulation. 1999; 100: 483-489
        • Ban Y.
        • Watanabe T.
        • Miyazaki A.
        • Nakano Y.
        • Tobe T.
        • Idei T.
        • et al.
        Impact of increased plasma serotonin levels and carotid atherosclerosis on vascular dementia.
        Atherosclerosis. 2007; 195: 153-159
        • Sugiura T.
        • Dohi Y.
        • Takase H.
        • Yamashita S.
        • Tanaka S.
        • Kimura G.
        Increased reactive oxygen metabolites is associated with cardiovascular risk factors and vascular endothelial damage in middle-aged Japanese subjects.
        Vasc. Health Risk Manag. 2011; 7: 475-482
        • Sugiura T.
        • Dohi Y.
        • Hirowatari Y.
        • Yamashita S.
        • Ohte N.
        • Kimura G.
        • et al.
        Cigarette smoking induces vascular damage and persistent elevation of plasma serotonin unresponsive to 8 weeks of smoking cessation.
        Int. J. Cardiol. 2013; 166: 748-749
        • Hirowatari Y.
        • Hara K.
        • Shimura Y.
        • Takahashi H.
        Serotonin levels in platelet-poor plasma and whole blood from healthy subjects: relationship with lipid markers and coronary heart disease risk score.
        J. Atheroscler. Thromb. 2011; 18: 874-882
        • Vanhoutte P.M.
        • Shimokawa H.
        • Tang E.H.
        • Feletou M.
        Endothelial dysfunction and vascular disease.
        Acta Physiol. (Oxf). 2009; 196: 193-222
        • Higashi Y.
        • Noma K.
        • Yoshizumi M.
        • Kihara Y.
        Endothelial function and oxidative stress in cardiovascular diseases.
        Circ. J. 2009; 73: 411-418
        • Deanfield J.E.
        • Halcox J.P.
        • Rabelink T.J.
        Endothelial function and dysfunction: testing and clinical relevance.
        Circulation. 2007; 115: 1285-1295
        • Dohi Y.
        • Takase H.
        • Sato K.
        • Ueda R.
        Association among C-reactive protein, oxidative stress, and traditional risk factors in healthy Japanese subjects.
        Int. J. Cardiol. 2007; 115: 63-66
        • Cai H.
        • Harrison D.G.
        Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress.
        Circ. Res. 2000; 87: 840-844
        • Shimamoto K.
        • Ando K.
        • Fujita T.
        • Hasebe N.
        • Higaki J.
        • Horiuchi M.
        • et al.
        Japanese Society of hypertension committee for guidelines for the management of hypertension. The Japanese Society of hypertension guidelines for the management of hypertension (JSH 2014).
        Hypertens. Res. 2014; 37: 253-392
        • Teramoto T.
        • Sasaki J.
        • Ueshima H.
        • Egusa G.
        • Kinoshita M.
        • Shimamoto K.
        • et al.
        Japan Atherosclerosis Society (JAS) Committee for Epidemiology and Clinical Management of Atherosclerosis. Diagnostic criteria for dyslipidemia. Executive summary of Japan Atherosclerosis Society (JAS) guideline for diagnosis and prevention of atherosclerotic cardiovascular diseases for Japanese.
        J. Atheroscler. Thromb. 2007; 14: 155-158
        • Hirowatari Y.
        • Hara K.
        • Kamihata H.
        • Iwasaka T.
        • Takahashi H.
        High-performance liquid chromatographic method with column-switching and post-column reaction for determination of serotonin levels in platelet-poor plasma.
        Clin. Biochem. 2004; 37: 191-197
        • Banes A.
        • Florian J.A.
        • Watts S.W.
        Mechanisms of 5-hydroxytryptamine (2A) receptor activation of the mitogen-activated protein kinase pathway in vascular smooth muscle.
        J. Pharmacol. Exp. Ther. 1999; 291: 1179-1187
        • Hamburg N.M.
        • Palmisano J.
        • Larson M.G.
        • Sullivan L.M.
        • Lehman B.T.
        • Vasan R.S.
        • et al.
        Relation of brachial and digital measures of vascular function in the community: the Framingham heart study.
        Hypertension. 2011; 57: 390-396
        • Schnabel R.B.
        • Schulz A.
        • Wild P.S.
        • Sinning C.R.
        • Wilde S.
        • Eleftheriadis M.
        • et al.
        Noninvasive vascular function measurement in the community: cross-sectional relations and comparison of methods.
        Circ. Cardiovasc Imaging. 2011; 4: 371-380