Heart angiotensin II-induced cardiomyocyte hypertrophy suppresses coronary angiogenesis and progresses diabetic cardiomyopathy

Autor: Genro Fujisawa, Yuko Watanabe, Nobuhiro Sasaki, Mariko Kimura, Eiji Kobayashi, Kazuyuki Shimada, Takahiro Masuda, Takahisa Kobayashi, Takashi Murakami, Eiji Kusano, Mutsuko Nonaka-Sarukawa, Masami Shinohara, Yoshitaka Iwazu, Shigeaki Muto
Rok vydání: 2012
Předmět:
Male
Vascular Endothelial Growth Factor A
medicine.medical_specialty
Physiology
Angiogenesis
Diabetic Cardiomyopathies
Neovascularization
Physiologic
Tetrazoles
Apoptosis
Rats
Mutant Strains
Muscle hypertrophy
Neovascularization
Rats
Sprague-Dawley
Thrombospondin 1
chemistry.chemical_compound
Angiotensin Receptor Antagonists
Ventricular Dysfunction
Left
Physiology (medical)
Internal medicine
Diabetic cardiomyopathy
medicine
Animals
Myocytes
Cardiac
Olmesartan Medoxomil
business.industry
Angiotensin II
Imidazoles
Kinase insert domain receptor
Hypertrophy
medicine.disease
Rats
Vascular endothelial growth factor
Disease Models
Animal
Endocrinology
chemistry
Diabetes Mellitus
Type 2
Hypertrophy
Left Ventricular
medicine.symptom
Cardiology and Cardiovascular Medicine
Olmesartan
business
medicine.drug
Zdroj: American journal of physiology. Heart and circulatory physiology. 302(9)
ISSN: 1522-1539
Popis: To examine whether and how heart ANG II influences the coordination between cardiomyocyte hypertrophy and coronary angiogenesis and contributes to the pathogenesis of diabetic cardiomyopathy, we used Spontaneously Diabetic Torii (SDT) rats treated without and with olmesartan medoxomil (an ANG II receptor blocker). In SDT rats, left ventricular (LV) ANG II, but not circulating ANG II, increased at 8 and 16 wk after diabetes onset. SDT rats developed LV hypertrophy and diastolic dysfunction at 8 wk, followed by LV systolic dysfunction at 16 wk, without hypertension. The SDT rat LV exhibited cardiomyocyte hypertrophy and increased hypoxia-inducible factor-1α expression at 8 wk and to a greater degree at 16 wk and interstitial fibrosis at 16 wk only. In SDT rats, coronary angiogenesis increased with enhanced capillary proliferation and upregulation of the angiogenic factor VEGF at 8 wk but decreased VEGF with enhanced capillary apoptosis and suppressed capillary proliferation despite the upregulation of VEGF at 16 wk. In SDT rats, the phosphorylation of VEGF receptor-2 increased at 8 wk alone, whereas the expression of the antiangiogenic factor thrombospondin-1 increased at 16 wk alone. All these events, except for hyperglycemia or blood pressure, were reversed by olmesartan medoxomil. These results suggest that LV ANG II in SDT rats at 8 and 16 wk induces cardiomyocyte hypertrophy without affecting hyperglycemia or blood pressure, which promotes and suppresses coronary angiogenesis, respectively, via VEGF and thrombospondin-1 produced from hypertrophied cardiomyocytes under chronic hypoxia. Thrombospondin-1 may play an important role in the progression of diabetic cardiomyopathy in this model.
Databáze: OpenAIRE
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