Systemic MCP1/CCR2 blockade and leukocyte specific MCP1/CCR2 inhibition affect aortic aneurysm formation differently
| Autor: | Kensuke Egashira, Goran Marinković, Vivian de Waard, Margreet R. de Vries, Theo J.C. Van Berkel, Erik A.L. Biessen, Saskia C.A. de Jager, Ilze Bot, Sara Talib, Paul H.A. Quax |
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| Přispěvatelé: | Pathologie, RS: CARIM School for Cardiovascular Diseases, ACS - Amsterdam Cardiovascular Sciences, Medical Biochemistry |
| Rok vydání: | 2009 |
| Předmět: |
Apolipoprotein E
Pathology medicine.medical_specialty CCR2 Physiology Receptors CCR2 Affect (psychology) Lesion Aortic aneurysm Mice Apolipoproteins E Internal medicine Leukocytes STAT5 Transcription Factor Medicine Animals RNA Small Interfering Receptor STAT5 Chemokine CCL2 Bone Marrow Transplantation Pharmacology Wound Healing biology business.industry medicine.disease Atherosclerosis Aneurysm Surgery Blockade medicine.anatomical_structure MCP1 Immunology Cardiology biology.protein Molecular Medicine Bone marrow medicine.symptom Cardiology and Cardiovascular Medicine business Aortic Aneurysm Abdominal |
| Zdroj: | Atherosclerosis, 211(1), 84-89. Elsevier Ireland Ltd |
| ISSN: | 1879-1484 0021-9150 |
| Popis: | Objective: CCR2, the receptor for monocyte chemoattractant protein 1 (MCP1), is involved in atherosclerosis and abdominal aortic aneurysms (AAAs). Here, we explored the potential beneficial blockade of the MCP1/CCR2 pathway. Methods: We applied an AAA model in aging apolipoprotein E deficient mice with pre-existing atherosclerotic lesions. These mice were subjected to two therapeutic strategies. First, a dominant negative form of MCP1 was overexpressed in femoral muscles, resulting in circulating levels of MCP1-7ND (7ND), competing with native MCP1. In the second approach, bone marrow transplantation was performed using bone marrow cells that were infected with a lentiviral construct containing siRNA for CCR2, to specifically inhibit only leukocyte CCR2 expression. Results: Both strategies did not influence lesion size of the advanced atherosclerotic plaques. However, 7ND induced a more fibrous plaque phenotype. Yet, surprisingly a trend in increased number and severity of AAA was observed in the 7ND group. Smooth muscle cells in the aneurysm showed decreased phosphorylated signal transducer and activator of transcription five (STAT5, P |
| Databáze: | OpenAIRE |
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