Abstract | BACKGROUND: METHODS AND RESULTS: When exposed to hypoxia, rat cardiomyocytes showed increased expression of endostatin. After MI induction in the rat MI model, endostatin expression was upregulated in cardiomyocytes, and serum endostatin levels were significantly elevated. Anti- endostatin antibody treatment resulted in significantly higher mortality of MI rats than controls. The MI rats with endostatin neutralization displayed adverse LV remodeling and severe heart failure compared with control MI rats. Although angiogenesis was increased, tissue remodeling and interstitial fibrosis were further exaggerated in post-MI hearts by endostatin neutralization. Furthermore, the expression and protease activity of matrix metalloproteinases -2 and -9, and of angiotensin-converting enzyme were markedly elevated by endostatin neutralization. CONCLUSIONS: Neutralization of endostatin worsens the symptoms and outcomes of MI in a rat model. The results imply that endogenous endostatin/ collagen XVIII may suppress aberrant LV remodeling and heart failure after MI. (Circ J 2010; 74: 109 - 119).
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Authors | Kazuya Isobe, Keiji Kuba, Yasuhiro Maejima, Jun-Ichi Suzuki, Shunichiro Kubota, Mitsuaki Isobe |
Journal | Circulation journal : official journal of the Japanese Circulation Society
(Circ J)
Vol. 74
Issue 1
Pg. 109-19
(Jan 2010)
ISSN: 1347-4820 [Electronic] Japan |
PMID | 19966499
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Collagen Type XVIII
- Endostatins
- Immunoglobulin G
- Peptidyl-Dipeptidase A
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
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Topics |
- Animals
- Cells, Cultured
- Collagen Type XVIII
(antagonists & inhibitors, immunology, physiology)
- Disease Models, Animal
- Endostatins
(antagonists & inhibitors, immunology, physiology)
- Heart Failure
(metabolism, physiopathology)
- Immunoglobulin G
(pharmacology)
- Male
- Matrix Metalloproteinase 2
(metabolism)
- Matrix Metalloproteinase 9
(metabolism)
- Mice
- Myocardial Infarction
(metabolism, physiopathology)
- Myocytes, Cardiac
(drug effects, metabolism, pathology)
- Neovascularization, Physiologic
(drug effects, physiology)
- Peptidyl-Dipeptidase A
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Rats, Wistar
- Ventricular Remodeling
(physiology)
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