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Role of Serotonin in Angiogenesis in Diabetes

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Biochemical Basis and Therapeutic Implications of Angiogenesis

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 6))

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Abstract

Serotonin (5-hydroxytryptamine, 5-HT) is a monoaminergic neurotransmitter synthesized from tryptophan, which is one of the essential amino acids, by mostly enterochromaffin cells in the gut. 5-HT receptors (15 subtypes) are distributed in tissues throughout the body and have diverse effects and play a crucial role in central and peripheral functions. The cardiovascular system is no exception; most of the 5-HT receptor subtypes have been shown to exist and be involved in cardiovascular regulation in both physiological and pathological conditions. Particularly in the vasculature, 5-HT is known to regulate vascular tonus and vascular cell proliferation by the balance of smooth muscle and endothelial 5-HT receptors. Under pathological conditions like diabetes mellitus (DM) and peripheral artery disease (PAD), serum 5-HT level is known to increase and is the hallmark of both pathological conditions. In these conditions, contractile activity of smooth muscle 5-HT2A receptor is increased; thus, 5-HT-mediated vasodilation and endothelial proliferation are inhibited, leading to diminished angiogenesis and peripheral circulation. However, blockade of 5-HT2A by clinically available drugs in a diabetic state enhances angiogenesis and vasodilation. As selective 5-HT2A blocker is widely used to treat PAD patients in clinical practice, the enhancement of angiogenesis, in addition to inhibition of vasoconstriction, might provide a unique treatment combination for therapeutic angiogenesis under a diabetic condition.

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Authors and Affiliations

  1. Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Masaaki Iwabayashi, Yoshiaki Taniyama, Junya Azuma, Fumihiro Sanada, Kazuma Iekushi & Ryuichi Morishita

  2. Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan

    Yoshiaki Taniyama, Junya Azuma, Kazuma Iekushi & Hiromi Rakugi

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  1. Masaaki Iwabayashi
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  2. Yoshiaki Taniyama
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  4. Fumihiro Sanada
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Correspondence to Ryuichi Morishita .

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  1. Div. of Cardiovascular Medicine, UAMS, Little Rock, AR, USA, 4301 W Markham, Little Rock, 72205, Arkansas, USA

    Jawahar L. Mehta

  2. Institute of Cardiovascular Sciences, St. Boniface Hosp. Research, Univ. of Ma, 351 Tache Avenue, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

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Iwabayashi, M. et al. (2013). Role of Serotonin in Angiogenesis in Diabetes. In: Mehta, J., Dhalla, N. (eds) Biochemical Basis and Therapeutic Implications of Angiogenesis. Advances in Biochemistry in Health and Disease, vol 6. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5857-9_13

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