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Impact of increased plasma serotonin levels and carotid atherosclerosis on vascular dementia

      Abstract

      Serotonin (5-HT), a potent vasoconstrictor in the large cerebral arteries, is considered to play a key role in atherothrombosis and to be implicated in ischemic cerebrovascular events followed by delayed neuronal death. The present study aims at evaluating the relationship between plasma levels of 5-HT and vascular dementia (VaD) caused by stroke or atherosclerotic small vessel disease. Carotid artery intima-media thickness (IMT), plaques, plasma 5-HT levels and atherosclerotic parameters were determined in 20 patients with VaD and 40 age-matched controls. Age, gender, body mass index, systolic and diastolic blood pressure, fasting plasma glucose levels and serum levels of insulin, triglycerides, high-density lipoprotein cholesterol, leptin, adiponectin and interleukin-6 and plasma levels of plasminogen activator inhibitor-1 were not significantly different between the two groups. Serum levels of insulin-like growth factor-1 (IGF-1) were significantly lower in VaD patients than in controls. Plasma 5-HT levels, serum levels of hepatocyte growth factor (HGF), low-density lipoprotein (LDL) cholesterol and high-sensitive C-reactive protein (hs-CRP), max IMT and plaque frequency were significantly greater in VaD patients than in controls. There was a significant positive correlation of max IMT with 5-HT or HGF levels. Multiple logistic regression analysis revealed that increased plasma levels of 5-HT and carotid plaque prevalence had significantly independent association with VaD as compared with serum levels of IGF-1, HGF, LDL cholesterol and hs-CRP. These results suggest that increased plasma levels of 5-HT and carotid atherosclerotic plaques may be involved in the pathogenesis and progression of VaD.

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      References

        • Yanagihara T.
        Vascular dementia in Japan.
        Ann NY Acad Sci. 2002; 977: 24-28
        • Watanabe T.
        • Koba S.
        • Katagiri T.
        • et al.
        Small dense low-density lipoprotein and carotid atherosclerosis in relation to vascular dementia.
        Metabolism. 2004; 53: 476-482
        • Yamamoto H.
        • Watanabe T.
        • Miyazaki A.
        • et al.
        High prevalence of Chlamydia pneumoniae antibodies and increased high-sensitive C-reactive protein in patients with vascular dementia.
        J Am Geriatric Soc. 2005; 53: 583-589
        • Watanabe T.
        • Miyazaki A.
        • Yamamoto H.
        • et al.
        Relation of serum insulin-like growth factor-1 levels to Alzheimer's disease and vascular dementia.
        J Am Geriatr Soc. 2005; 53: 1748-1753
        • Watanabe T.
        • Yamamoto H.
        • Idei T.
        • Iguchi T.
        • Katagiri T.
        Influence of insulin-like growth factor-1 and hepatocyte growth factor on carotid atherosclerosis and cognitive function in the elderly.
        Dement Geriatr Cogn Disord. 2004; 18: 67-74
        • Vikenes K.
        • Farstad M.
        • Nordrehaug J.E.
        Serotonin is associated with coronary artery disease and cardiac events.
        Circulation. 1999; 100: 483-489
        • Doggrell S.A.
        Sarpogrelate: cardiovascular and renal clinical potential.
        Expert Opin Investig Drugs. 2004; 13: 865-874
        • Pakala R.
        • Willerson J.T.
        • Benedict C.R.
        Mitogenic effect of serotonin on vascular endothelial cells.
        Circulation. 1994; 90: 1919-1926
        • Pakala R.
        • Willerson J.T.
        • Benedict C.
        Effect of serotonin, thromboxane A2, and specific receptor antagonists on vascular smooth muscle cell proliferation.
        Circulation. 1997; 96: 2280-2286
        • Yamakawa J.
        • Takahashi T.
        • Saegusa S.
        • et al.
        Effect of the serotonin blocker sarpogrelate on circulating interleukin-18 levels in patients with diabetes and arteriosclerosis obliterans.
        J Int Med Res. 2004; 32: 166-169
        • Watanabe T.
        • Pakala R.
        • Koba S.
        • Katagiri T.
        • Benedict C.R.
        Lysophosphatidylcholine and reactive oxygen species mediate the synergistic effect of mildly oxidized LDL with serotonin on vascular smooth muscle cell proliferation.
        Circulation. 2001; 103: 1440-1445
        • Watanabe T.
        • Pakala R.
        • Katagiri T.
        • Benedict C.R.
        Lipid peroxidation product 4-hydroxy-2-nonenal acts synergistically with serotonin in inducing vascular smooth muscle cell proliferation.
        Atherosclerosis. 2001; 155: 37-44
        • Pakala R.
        • Benedict C.
        Synergy between thrombin and serotonin in inducing vascular smooth muscle cell proliferation.
        J Lab Clin Med. 1999; 134: 659-667
        • Watanabe T.
        • Pakala R.
        • Katagiri T.
        • Benedict C.R.
        Angiotensin II and serotonin potentiate endothelin-1-induced vascular smooth muscle cell proliferation.
        J Hypertens. 2001; 19: 731-739
        • Watanabe T.
        • Pakala R.
        • Katagiri T.
        • Benedict C.R.
        Synergistic effect of urotensin II with serotonin on vascular smooth muscle cell proliferation.
        J Hypertens. 2001; 19: 2191-2196
        • Watanabe T.
        • Pakala R.
        • Katagiri T.
        • Benedict C.R.
        Monocyte chemotactic protein 1 amplifies serotonin-induced vascular smooth muscle cell proliferation.
        J Vasc Res. 2001; 38: 341-349
        • Suguro T.
        • Watanabe T.
        • Miyazaki A.
        • et al.
        Serotonin acts as an up-regulator of acyl-coenzyme A: cholesterol acyltransferase-1 in human monocyte-macrophages.
        Atherosclerosis. 2006; 186: 275-281
        • Ito T.
        • Ikeda U.
        • Shimpo M.
        • Yamamoto K.
        • Shimada K.
        Serotonin increases interleukin-6 synthesis in human vascular smooth muscle cells.
        Circulation. 2000; 102: 2522-2527
        • Roman G.C.
        • Tatemichi T.K.
        • Erkinjuntti T.
        • et al.
        Vascular dementia: diagnostic criteria for research studies: report of the NINDS-AIREN International Workshop.
        Neurology. 1993; 43: 250-260
      1. Suguro T, Watanabe T, Kodate S, et al. Increased human urotensin II levels are correlated with carotid atherosclerosis in essential hypertension. Am J Hypertens 2006, in press.

        • Arwert L.I.
        • Deijen J.B.
        • Drent M.L.
        The relation between insulin-like growth factor I levels and cognition in healthy elderly: a meta-analysis.
        Growth Horm IGF Res. 2005; 15: 416-422
        • Matsumori A.
        • Takano H.
        • Obata J.E.
        • et al.
        Circulating hepatocyte growth factor as a diagnostic marker of thrombus formation in patients with cerebral infarction.
        Circ J. 2002; 66: 216-218
        • Kuo H.K.
        • Yen C.J.
        • Chang C.H.
        • et al.
        Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis.
        Lancet Neurol. 2005; 4: 371-380
        • Roman G.C.
        Vascular dementia prevention: a risk factor analysis.
        Cerebrovasc Dis. 2005; 20: 91-100
        • Bonvento G.
        • MacKenzie E.T.
        • Edvinsson L.
        Serotonergic innervation of the cerebral vasculature: relevance to migraine and ischaemia.
        Brain Res. 1991; 16: 257-263
        • Wiernsperger N.
        Serotonin 5-HT2 receptors and brain circulation.
        J Cardiovasc Pharmacol. 1990; 16: S20-S24
        • Hansson G.
        • Alafuzoff I.
        • Winblad B.
        • Marcusson J.
        Intact brain serotonin system in vascular dementia.
        Dementia. 1996; 7: 196-200
        • Wester P.
        • Dietrich W.D.
        • Prado R.
        • Watson B.D.
        • Globus M.Y.T.
        Serotonin release into plasma during common carotid artery thrombosis in rats.
        Stroke. 1992; 23: 870-875
        • Globus M.Y.
        • Wester P.
        • Busto R.
        • Dietrich W.D.
        Ischemia-induced extracellular release of serotonin plays a role in CA1 neuronal cell death in rats.
        Stroke. 1992; 23: 1595-1601
        • Klisch J.
        • Bode-Greuel K.M.
        Ketanserin reduces neuronal calcium accumulation and cell death in the hippocampus of the Mongolian gerbil after transient forebrain ischemia.
        Brain Res. 1992; 578: 1-7
        • Buhot M.C.
        • Martin S.
        • Segu L.
        Role of serotonin in memory impairment.
        Ann Med. 2000; 32: 210-221
        • Meneses A.
        Involvement of 5-HT (2A/2B/2C) receptors on memory formation: simple agonism, antagonism, or inverse agonism?.
        Cell Mol Neurobiol. 2002; 22: 675-688
        • Spigset O.
        • Wilhelmsson C.
        • Mjorndal T.
        • Eriksson S.
        Serotonin 5-HT2A receptor binding in platelets from patients with Alzheimer's disease or vascular dementia.
        Int Psychogeriatr. 2000; 12: 537-545
        • Benedict C.R.
        • Mathew B.
        • Rex K.A.
        • Cartwright J.
        • Sordahl L.A.
        Correlation of plasma serotonin changes with platelet aggregation in an in vivo dog model of spontaneous occlusive coronary thrombus formation.
        Circ Res. 1986; 58: 58-67
        • Golino P.
        • Piscione F.
        • Benedict C.R.
        • et al.
        Local effect of serotonin released during coronary angioplasty.
        New Engl J Med. 1994; 330: 523-528
        • Leosco D.
        • Fineschi M.
        • Pierli C.
        • et al.
        Intracoronary serotonin release after high-pressure coronary stenting.
        Am J Cardiol. 1999; 84: 1317-1322
        • Tamura K.
        • Kanzaki T.
        • Saito Y.
        • et al.
        Serotonin (5-hydroxytryptamine, 5-HT) enhances migration of rat aortic smooth muscle cell through 5-HT2 receptors.
        Atherosclerosis. 1997; 132: 139-143
        • Banes A.
        • Florian J.A.
        • Watts S.W.
        Mechanisms of 5-hydroxytryptamine2A receptor activation of the mitogen-activated protein kinase pathway in vascular smooth muscle.
        J Pharmacol Exp Ther. 1999; 291: 1179-1187
        • Nishimura Y.
        Characterization of 5-hyroxytryptamine receptors mediating contractions in basilar arteries from stroke-prone spontaneously hypertensive rats.
        Br J Pharmacol. 1996; 117: 1325-1333
        • Gajdos M.
        • Spustova V.
        • Sebekova K.
        • Krivosikova Z.
        • Dzurik R.
        Effective long-term inhibition of thromboxane production but not of serotonin release in patients with coronary heart disease by 30 mg/d acetylsalicylic acid dosage.
        Prostaglandins Leukot Essent Fatty Acids. 1998; 59: 17-21