RRC ID |
38485
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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.
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タイトル |
Calcitonin gene-related peptide facilitates revascularization during hindlimb ischemia in mice.
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ジャーナル |
Am J Physiol Heart Circ Physiol
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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.
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巻・号 |
300(2)
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ページ |
H431-9
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公開日 |
2011-2-1
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DOI |
10.1152/ajpheart.00466.2010
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PII |
ajpheart.00466.2010
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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 |
|