Development of an experimentally useful model of acute myocardial infarction: 2/3 nephrectomized triple nitric oxide synthases-deficient mouse
| Autor: | Nobuyuki Yanagihara, Tomonori Igarashi, Masato Tsutsui, Hiroaki Masuzaki, Taro Uchida, Akihide Tanimoto, Yumiko Toyohira, Katsuhiko Noguchi, Masayuki Matsushita, Kumiko Arakaki, Junko Nakasone, Toshihiro Matsuzaki, Mayuko Sakanashi, Hiroaki Shimokawa, Yutaka Otsuji, Susumu Ueno, Yusuke Ohya, Yumi Furuno, Haruaki Kubota, Masahito Tamura, Mika Kina-Tanada, Shogo Ishiuchi |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Vascular smooth muscle Myocardial Infarction Nephrectomy Nitric oxide Pathogenesis chemistry.chemical_compound Irbesartan Internal medicine medicine Animals Amlodipine Myocardial infarction Progenitor cell Molecular Biology Mice Knockout business.industry medicine.disease Angiotensin II Disease Models Animal Oxidative Stress Endocrinology chemistry Nitric Oxide Synthase Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Journal of molecular and cellular cardiology. 77 |
| ISSN: | 1095-8584 |
| Popis: | We investigated the effect of subtotal nephrectomy on the incidence of acute myocardial infarction (AMI) in mice deficient in all three nitric oxide synthases (NOSs). Two-thirds nephrectomy (NX) was performed on male triple NOSs −/− mice. The 2/3NX caused sudden cardiac death due to AMI in the triple NOSs −/− mice as early as 4 months after the surgery. The 2/3NX triple NOSs −/− mice exhibited electrocardiographic ST-segment elevation, reduced heart rate variability, echocardiographic regional wall motion abnormality, and accelerated coronary arteriosclerotic lesion formation. Cardiovascular risk factors (hypertension, hypercholesterolemia, and hyperglycemia), an increased number of circulating bone marrow-derived vascular smooth muscle cell (VSMC) progenitor cells (a pro-arteriosclerotic factor), and cardiac up-regulation of stromal cell-derived factor (SDF)-1α (a chemotactic factor of the progenitor cells) were noted in the 2/3NX triple NOSs −/− mice and were associated with significant increases in plasma angiotensin II levels (a marker of renin–angiotensin system activation) and urinary 8-isoprostane levels (a marker of oxidative stress). Importantly, combined treatment with a clinical dosage of an angiotensin II type 1 receptor blocker, irbesartan, and a calcium channel antagonist, amlodipine, markedly prevented coronary arteriosclerotic lesion formation and the incidence of AMI and improved the prognosis of those mice, along with ameliorating all those pro-arteriosclerotic parameters. The 2/3NX triple NOSs −/− mouse is a new experimentally useful model of AMI. Renin–angiotensin system activation, oxidative stress, cardiovascular risk factors, and SDF-1α-induced recruitment of bone marrow-derived VSMC progenitor cells appear to be involved in the pathogenesis of AMI in this model. |
| Databáze: | OpenAIRE |
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