RRC ID 38485
著者 Mishima T, Ito Y, Hosono K, Tamura Y, Uchida Y, Hirata M, Suzsuki T, Amano H, Kato S, Kurihara Y, Kurihara H, Hayashi I, Watanabe M, Majima M.
タイトル Calcitonin gene-related peptide facilitates revascularization during hindlimb ischemia in mice.
ジャーナル Am J Physiol Heart Circ Physiol
Abstract It is known that the neural system plays a fundamental role in neovascularization. A neuropeptide, calcitonin gene-related peptide (CGRP), is widely distributed in the central and peripheral neuronal systems. However, it remains to be elucidated the role of CGRP in angiogenesis during ischemia. The present study examined whether endogenous CGRP released from neuronal systems facilitates revascularization in response to ischemia using CGRP knockout mice (CGRP-/-). CGRP-/- or their wild-type littermates (CGRP+/+) were subjected to unilateral hindlimb ischemia. CGRP-/- exhibited impaired blood flow recovery from ischemia and decreased capillary density expressed in terms of the number of CD-31-positive cells in the ischemic tissues compared with CGRP+/+. In vivo microscopic studies showed that the functional capillary density in CGRP-/- was reduced. Hindlimb ischemia increased the expression of pro-CGRP mRNA and of CGRP protein in the lumbar dorsal root ganglia. Lack of CGRP decreased mRNA expression of growth factors, including CD31, vascular endothelial growth factor-A, basic fibroblast growth factor, and transforming growth factor-β, in the ischemic limb tissue. The application of CGRP enhanced the mRNA expression of CD31 and VEGF-A in human umbilical vein endothelial cells (HUVECs) and fibroblasts. Subcutaneous infusion of CGRP8-37, a CGRP antagonist, using miniosmotic pumps delayed angiogenesis and reduced the expression of proangiogenic growth factors during hindlimb ischemia. These results indicate that endogenous CGRP facilitates angiogenesis in response to ischemia. Targeting CGRP may provide a promising approach for controlling angiogenesis related to pathophysiological conditions.
巻・号 300(2)
ページ H431-9
公開日 2011-2-1
DOI 10.1152/ajpheart.00466.2010
PII ajpheart.00466.2010
PMID 21131474
MeSH Angiogenic Proteins / biosynthesis Animals Blood Pressure / genetics Blood Pressure / physiology Calcitonin Gene-Related Peptide / antagonists & inhibitors Calcitonin Gene-Related Peptide / genetics Calcitonin Gene-Related Peptide / pharmacology Calcitonin Gene-Related Peptide / physiology* Calcitonin Gene-Related Peptide Receptor Antagonists Cell Separation Ganglia, Spinal / cytology Heart Rate / genetics Heart Rate / physiology Hindlimb / blood supply* Humans Immunohistochemistry Ischemia / pathology* Laser-Doppler Flowmetry Male Mice Mice, Inbred C57BL Mice, Knockout Neovascularization, Physiologic / genetics* Neovascularization, Physiologic / physiology* Neurons / physiology Peptide Fragments / pharmacology Regional Blood Flow / genetics Regional Blood Flow / physiology Reverse Transcriptase Polymerase Chain Reaction
IF 3.864
引用数 35
WOS 分野 PHYSIOLOGY CARDIAC & CARDIOVASCULAR SYSTEMS PERIPHERAL VASCULAR DISEASE
リソース情報
ヒト・動物細胞