Apelin prevents aortic aneurysm formation by inhibiting macrophage inflammation

Autor: Yoko Kojima, Euan A. Ashley, Phillip Tsao, Geoffrey M. Schultz, Thomas Quertermous, Ronald L. Dalman, Nicholas J. Leeper, Maureen M. Tedesco, Ramendra K. Kundu
Rok vydání: 2009
Předmět:
Male
medicine.medical_specialty
Chemokine
Physiology
medicine.medical_treatment
Anti-Inflammatory Agents
Down-Regulation
Inflammation
Proinflammatory cytokine
Mice
Physiology (medical)
Internal medicine
Animals
Medicine
Aorta
Abdominal
Macrophage inflammatory protein
Ultrasonography
Aortitis
Pancreatic Elastase
biology
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Macrophages
Monocyte
Articles
Infusion Pumps
Implantable
Immunohistochemistry
Rats
Apelin
Mice
Inbred C57BL
Disease Models
Animal
Endocrinology
Cytokine
medicine.anatomical_structure
Immunology
NIH 3T3 Cells
biology.protein
Cytokines
Intercellular Signaling Peptides and Proteins
Tumor necrosis factor alpha
Chemokines
Inflammation Mediators
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Aortic Aneurysm
Abdominal
Zdroj: American Journal of Physiology-Heart and Circulatory Physiology. 296:H1329-H1335
ISSN: 1522-1539
0363-6135
Popis: Apelin is a potent inodilator with recently described antiatherogenic properties. We hypothesized that apelin might also attenuate abdominal aortic aneurysm (AAA) formation by limiting disease-related vascular wall inflammation. C57BL/6 mice implanted with osmotic pumps filled with apelin or saline were treated with pancreatic elastase to create infrarenal AAAs. Mice were euthanized for aortic PCR analysis or followed ultrasonographically and then euthanized for histological analysis. The cellular expression of inflammatory cytokines and chemokines in response to apelin was also assessed in cultured macrophages, smooth muscle cells, and fibroblasts. Apelin treatment resulted in diminished AAA formation, with a 47% reduction in maximal cross-sectional area (0.74 vs. 1.39 mm2, P < 0.03) and a 57% reduction in macrophage infiltrate (113 vs. 261.3 cells/high-power field, P < 0.0001) relative to the saline-treated group. Apelin infusion was also associated with significantly reduced aortic macrophage colony-stimulating factor expression and decreased monocyte chemattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, interleukin (IL)-6, and tumor necrosis factor (TNF)-α mean mRNA levels. Apelin stimulation of cultured macrophages significantly reduced MCP-1 and TNF-α mRNA levels relative to baseline (2.03- and 1.89-fold reduction, P < 0.03, respectively) but did not affect intimal adhesion molecule expression or medial or adventitial cell cytokine production. Apelin significantly reduces aneurysm formation in the elastase model of human AAA disease. The mechanism appears to be decreased macrophage burden, perhaps related to an apelin-mediated decrease in proinflammatory cytokine and chemokine activation.
Databáze: OpenAIRE
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