Nitrosonifedipine, a Photodegradation Product of Nifedipine, Suppresses Pharmacologically Induced Aortic Aneurysm Formation
| Autor: | Keisuke Ishizawa, Yuki Izawa-Ishizawa, Masaki Imanishi, Masanori Yoshizumi, Takumi Sakurada, Koichiro Tsuchiya, Masayuki Chuma, Hiromichi Fujino, Kenshi Takechi, Eriko Sairyo, Yusuke Kohara, Yasumasa Ikeda, Toshiaki Tamaki, Keijo Fukushima, Yoshito Zamami, Yuya Horinouchi |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Nifedipine Vascular Cell Adhesion Molecule-1 Inflammation Pharmacology medicine.disease_cause Antioxidants Cyclophilins Mice 03 medical and health sciences chemistry.chemical_compound Aortic aneurysm medicine.artery Human Umbilical Vein Endothelial Cells medicine Animals Humans Chemokine CCL2 Aorta Photolysis Cell adhesion molecule Angiotensin II Nitrotyrosine Endothelial Cells General Medicine biochemical phenomena metabolism and nutrition medicine.disease Antigens Differentiation Aortic Aneurysm Elastin Disease Models Animal Oxidative Stress 030104 developmental biology chemistry Aminopropionitrile cardiovascular system Matrix Metalloproteinase 2 medicine.symptom Reactive Oxygen Species Oxidative stress Nitroso Compounds medicine.drug |
| Zdroj: | Pharmacology. 102:287-299 |
| ISSN: | 1423-0313 0031-7012 |
| Popis: | Background/Aims: We have reported that nitrosonifedipine (NO-NIF), a photodegradation product of nifedipine, has strong antioxidant and endothelial protective effects, and can suppress several cardiovascular diseases in animal models. The objective of the present study was to investigate the effects of NO-NIF on aortic aneurysm formation. Methods: The mice were infused with β-aminopropionitrile for 2 weeks and angiotensin II for 6 weeks to induce aortic aneurysm formation. The oxidative stress was measured by dihydroethidium staining and nitrotyrosine staining. The expressions of inflammation-related genes were assessed by quantitative real-time PCR and immunohistochemical staining. To clarify the mechanisms of how NO-NIF suppresses vascular cell adhesion molecule (VCAM)-1, endothelial cells were used in in vitro system. Results: NO-NIF suppressed pharmacologically induced the aortic aneurysm formation and aortic expansion without blood pressure changes. NO-NIF suppressed elastin degradation and matrix metalloproteinase-2 mRNA expression. NO-NIF suppressed the reactive oxygen species-cyclophilin A positive feedback loop. Upregulated mRNA expressions of inflammation-related genes and endothelial VCAM-1 were suppressed by NO-NIF co-treatment in aortae. Conclusion: NO-NIF has the potential to be a new, nifedipine-derived therapeutic drug for suppressing aortic aneurysm formation by directly improving aortic structure with its strong ability to reduce oxidative stress and inflammation. |
| Databáze: | OpenAIRE |
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