Angiotensin II receptor antagonist attenuates expression of aging markers in diabetic mouse heart.
BACKGROUND
Diabetes mellitus is an independent risk factor for heart failure. Diabetes mellitus causes other age-related cardiovascular diseases. We assessed the hypothesis that hearts from diabetic animals are associated with accelerated aging processes. We also examined the effect of an angiotensin II receptor blocker (ARB) on the expression of senescence-associated molecules.


RESULTS
We administered an ARB (candesartan 10 mg/kg per day) or saline to diabetic db/db or control db/+ mice. The treatment was started when mice were 10-weeks-old, and continued for 15 weeks. Systolic function was impaired in db/db mice and candesartan improved cardiac function. The amount of phosphorylated Akt and S6 was decreased in saline-treated db/db mice, and candesartan treatment partially preserved phosphorylation. The amount of p21, p27, p53 or Rb was increased in the heart tissue of saline treated db/db mice. Candesartan treatment completely suppressed the increases of p21, p27, p53 and Rb.


CONCLUSIONS
An ARB improved cardiac function of diabetic animals, and this was accompanied by decreases of senescence-associated molecules in the myocardium. ARB may be a modality for heart failure patients with diabetes mellitus.
Department of Internal Medicine and Cardiology, Kitasato University School of Medicine, Sagamihara, Japan.
Rie
R
Kosugi
Tetsuo
T
Shioi
Kayo
K
Watanabe-Maeda
Yuki
Y
Yoshida
Keiko
K
Takahashi
Yoji
Y
Machida
Tohru
T
Izumi
D000375:Aging / Q000235:genetics*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D001713:Biphenyl Compounds; D001786:Blood Glucose / Q000032:analysis; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics*; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D004452:Echocardiography; D005786:Gene Expression Regulation / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009206:Myocardium / Q000737:chemistry; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000502:physiology; D016160:Retinoblastoma Protein / Q000235:genetics / Q000502:physiology; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D001786:Blood Glucose; D007328:Insulin; D018809:Proliferating Cell Nuclear Antigen; D016160:Retinoblastoma Protein; D013777:Tetrazoles; D016159:Tumor Suppressor Protein p53; C413374:p27 antigen; D051058:Oncogene Protein v-akt; D019893:Ribosomal Protein S6 Kinases; D020741:rho GTP-Binding Proteins; C081643:candesartan