Role of vascular endothelial growth factor-A in development of abdominal aortic aneurysm.

Abstract

AIMS:

Increased angiogenesis, chronic inflammation, and extracellular matrix degradation are the major pathological features of abdominal aortic aneurysm (AAA). We sought to elucidate the role of vascular endothelial growth factor (VEGF)-A, a potent angiogenic and proinflammatory factor, in the development of AAA.

METHODS AND RESULTS:

Human AAA samples showed increased VEGF-A expression, neovascularization, and macrophage infiltration compared with normal aortic walls. AAA was induced in mice by periaortic application of CaCl(2). AAA mice were treated with soluble VEGF-A receptor (sFlt)-1 or phosphate-buffered saline and sacrificed 6 weeks after the operation. Treatment with sFlt-1 resulted in reduced aneurysm size, restored wavy structure of the elastic lamellae, reduced Mac-2(+) monocytes/macrophages, CD3(+) T-lymphocytes, and CD31(+) vessels, and attenuated matrix metalloproteinase (MMP)-2 and 9 activity in periaortic tissue of AAA. Increased aortic mRNA expression of monocyte chemotactic protein-1, tumour necrosis factor-α, and intercellular adhesion molecule-1 in AAA was attenuated by sFlt-1 treatment.

CONCLUSION:

VEGF-A was overexpressed in the aortic wall of human and experimental AAA. Treatment with sFlt-1 inhibited AAA development in mice, in association with reduced neoangiogenesis, infiltration of inflammatory cells, MMP activity, and extracellular matrix degradation. These findings suggest a crucial role of VEGF-A in the development of AAA.

• Authors: Hidehiro Kaneko, Toshihisa Anzai, Toshiyuki Takahashi, Takashi Kohno, Masayuki Shimoda, Aya Sasaki, Hideyuki Shimizu, Toshiyuki Nagai, Yuichiro Maekawa, Koichi Yoshimura, Hiroki Aoki, Tsutomu Yoshikawa, Yasunori Okada, Ryohei Yozu, Satoshi Ogawa, Keiichi Fukuda
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 91 Issue 2 Pg. 358-67 (Jul 15 2011) ISSN: 1755-3245 [Electronic] England
• PMID: 21436157 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Inflammation Mediators
• RNA, Messenger
• Recombinant Proteins
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Flt1 protein, mouse
• Vascular Endothelial Growth Factor Receptor-1
• Matrix Metalloproteinase 2
• Mmp2 protein, mouse
• Matrix Metalloproteinase 9
• Mmp9 protein, mouse
• Calcium Chloride

Topics

• Aged
• Analysis of Variance
• Animals
• Aorta, Abdominal (drug effects, immunology, metabolism, pathology)
• Aortic Aneurysm, Abdominal (chemically induced, drug therapy, immunology, metabolism, pathology, physiopathology)
• Aortography (methods)
• Calcium Chloride
• Chi-Square Distribution
• Cytokines (genetics)
• Disease Models, Animal
• Female
• Hemodynamics
• Humans
• Inflammation Mediators (metabolism)
• Injections, Intraperitoneal
• Macrophages (immunology, metabolism)
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Neovascularization, Pathologic (metabolism, prevention & control)
• RNA, Messenger (metabolism)
• Recombinant Proteins (administration & dosage)
• Time Factors
• Tomography, X-Ray Computed
• Up-Regulation
• Vascular Endothelial Growth Factor A (blood, genetics)
• Vascular Endothelial Growth Factor Receptor-1 (administration & dosage)