Neuropeptides and Angiogenesis
Neuropeptides are one of the most conserved proteins across different species and are ubiquitously expressed in different organs. In the peripheral nervous system, neuropeptides are secreted by the sensory and autonomic nerves and participate in a wide ra
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Neuropeptides and Angiogenesis Leena Pradhan-Nabzdyk and Christoph Nabzdyk
Abstract Neuropeptides are one of the most conserved proteins across different species and are ubiquitously expressed in different organs. In the peripheral nervous system, neuropeptides are secreted by the sensory and autonomic nerves and participate in a wide range of functions including immune surveillance, cardiovascular homeostasis, regulation of endocrine function, cytokine and growth factor release, and importantly angiogenesis. Neuropeptides including neuropeptide Y, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, and somatostatin (SS) are some of the neuropeptides that have been investigated regarding their role in modulating the vascular system and angiogenesis. All of these neuropeptides are pro-angiogenic except SS, which has anti-angiogenic properties. This chapter aims to present up-to-date evidence on the various mechanisms of action of the aforementioned neuropeptides and their clinical implications. Keywords Neuropeptides • Wound healing • Cancer • Ischemia
L. Pradhan-Nabzdyk, Ph.D. (*) Department of Surgery, Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Dana Building 805, Boston, MA 02215, USA e-mail: [email protected] C. Nabzdyk Department of Surgery, Tufts Medical Center, Boston, MA USA
J.L. Mehta and N.S. Dhalla (eds.), Biochemical Basis and Therapeutic Implications of Angiogenesis, Advances in Biochemistry in Health and Disease 6, DOI 10.1007/978-1-4614-5857-9_4, © Springer Science+Business Media New York 2013
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Introduction
Neuropeptides are some of the most conserved and abundant peptides in vertebrates and function as neurotransmitters or neuromodulators or both within the central nervous system (CNS) and peripheral nervous system (PNS). Neuropeptides released from the PNS participate in major physiological functions ranging from cardiovascular homeostasis and gastrointestinal motility to immune cell trafficking. Neuropeptides including neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and somatostatin (SS) have emerged as important regulators that affect the vascular system by modulating the vascular tone, angiogenesis, and vascular remodeling [1–10]. Most of these neuropeptides are pro-angiogenic, with the exception of SS, which has anti-angiogenic properties. Numerous studies have investigated the role of neuropeptides in angiogenesis, but there has been limited success in the development of neuropeptide-based therapies targeting angiogenesis. While some of the neuropeptides or neuropeptide-based therapeutics is in the pipeline for treatment of other diseases, so far, SS analogues are the only neuropeptide-based therapies used for modulating/inhibiting angiogenesis in cancer. This suggests that the ubiquitous and complicated neuropeptide signaling system in the vasculature nee
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