PMID- 24256203 OWN - NLM STAT- MEDLINE DCOM- 20140320 LR - 20220311 IS - 1470-8736 (Electronic) IS - 0143-5221 (Linking) VI - 126 IP - 9 DP - 2014 May TI - Suppression of abdominal aortic aneurysm formation by inhibition of prolyl hydroxylase domain protein through attenuation of inflammation and extracellular matrix disruption. PG - 671-8 LID - 10.1042/CS20130435 [doi] AB - In the present study we sought to determine the effect of CoCl2, an inhibitor of PHD (prolyl hydroxylase domain protein), on the development of AAA (abdominal aortic aneurysm). AAA was induced in C57BL/6 mice by periaortic application of CaCl2 (AAA group). NaCl (0.9%)-treated mice were used as a sham control (SHAM group). Mice were treated with 0.05% CoCl2 in the drinking water (AAA/CoCl2 group). At 1 and 6 weeks after the operation, aortic tissue was excised for further examination. After 6 weeks of CaCl2 treatment, aortic diameter and macrophage infiltration into the aortic adventitia were increased in the AAA group compared with the SHAM group. Treatment with CoCl2 reduced the aneurysmal size and macrophage infiltration compared with the AAA group. Aortic expression of inflammatory cytokines and MCP-1 (monocyte chemoattractant protein-1) and the activities of MMP-9 (matrix metalloproteinase-9) and MMP-2 were enhanced in the AAA group and attenuated in the AAA/CoCl2 group. Expression of cytokines and the activities of MMPs were already increased after 1 week of CaCl2 treatment, but were suppressed by CoCl2 treatment in association with reduced NF-kappaB (nuclear factor kappaB) phosphorylation. Treatment with CoCl2 in mice prevented the development of CaCl2-induced AAA in association with reduced inflammation and ECM (extracellular matrix) disruption. The results of the present study suggest that PHD plays a critical role in the development of AAA and that there is a therapeutic potential for PHD inhibitors in the prevention of AAA development. FAU - Watanabe, Aya AU - Watanabe A AD - *Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Ichiki, Toshihiro AU - Ichiki T FAU - Sankoda, Chikahiro AU - Sankoda C AD - *Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Takahara, Yusuke AU - Takahara Y AD - *Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Ikeda, Jiro AU - Ikeda J AD - *Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Inoue, Eriko AU - Inoue E AD - *Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Tokunou, Tomotake AU - Tokunou T AD - *Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Kitamoto, Shiro AU - Kitamoto S FAU - Sunagawa, Kenji AU - Sunagawa K AD - *Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Clin Sci (Lond) JT - Clinical science (London, England : 1979) JID - 7905731 RN - 0 (Cytokines) RN - 0 (Enzyme Inhibitors) RN - 0 (Inflammation Mediators) RN - 0 (Rela protein, mouse) RN - 0 (Transcription Factor RelA) RN - 3G0H8C9362 (Cobalt) RN - EC 1.11.1.6 (Catalase) RN - EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases) RN - EC 1.15.1.1 (Sod1 protein, mouse) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 1.15.1.1 (Superoxide Dismutase-1) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.24 (Mmp2 protein, mouse) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - EC 3.4.24.35 (Mmp9 protein, mouse) RN - EVS87XF13W (cobaltous chloride) RN - M4I0D6VV5M (Calcium Chloride) SB - IM MH - Animals MH - Aorta, Abdominal/*drug effects/enzymology/immunology/pathology MH - Aortic Aneurysm, Abdominal/chemically induced/enzymology/immunology/pathology/*prevention & control MH - Aortitis/chemically induced/enzymology/immunology/pathology/*prevention & control MH - Calcium Chloride MH - Catalase/metabolism MH - Cobalt/*pharmacology MH - Cytokines/metabolism MH - Disease Models, Animal MH - Enzyme Inhibitors/*pharmacology MH - Extracellular Matrix/*metabolism MH - Hypoxia-Inducible Factor-Proline Dioxygenases/*antagonists & inhibitors/metabolism MH - Inflammation Mediators/metabolism MH - Macrophages/drug effects/immunology MH - Matrix Metalloproteinase 2/metabolism MH - Matrix Metalloproteinase 9/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Phosphorylation MH - Superoxide Dismutase/metabolism MH - Superoxide Dismutase-1 MH - Time Factors MH - Transcription Factor RelA/metabolism EDAT- 2013/11/22 06:00 MHDA- 2014/03/22 06:00 CRDT- 2013/11/22 06:00 PHST- 2013/11/22 06:00 [entrez] PHST- 2013/11/22 06:00 [pubmed] PHST- 2014/03/22 06:00 [medline] AID - CS20130435 [pii] AID - 10.1042/CS20130435 [doi] PST - ppublish SO - Clin Sci (Lond). 2014 May;126(9):671-8. doi: 10.1042/CS20130435.