Characterization of an animal model of postmenopausal cardiac hypertrophy and novel mechanisms responsible for cardiac decompensation using ovariectomized pressure-overloaded rats.
OBJECTIVE
The development of animal models of cardiovascular disease are critical to define pathophysiological mechanisms and to advance diagnosis and therapy. The lack of a suitable animal model represents a failure to define the mechanisms responsible for postmenopausal myocardial hypertrophy in hypertension and adverse cardiac remodeling.


METHODS
In this review, we presented a rat model of postmenopausal myocardial hypertrophy, with particular focus on the similarities between the animal model and postmenopausal women regarding myocardial function as well as molecular and subcellular mechanisms. To elucidate the molecular mechanism of left ventricular (LV) hypertrophy and remodeling in postmenopausal women, we analyzed myocardial hypertrophy as well as cardiac function and hypertrophy-related protein expression in ovariectomized (OVX) and pressure overloaded (PO) rats.


RESULTS
The model is characterized by depletion of serum estrogen and increased heart-to-body weight and lung-to-body weight ratios. Moreover, the OVX-PO rats also show increased mean arterial blood pressure, LV end-diastolic pressure, LV developed pressure, and maximal rates of LV contraction and relaxation compared with the OVX group. Importantly, Akt activity was largely attenuated, and both endothelial nitric oxide synthase expression and activity were markedly reduced in the OVX-PO group. Finally, significant increased mortality was observed in the OVX-PO group after chronic isoproterenol administration.


CONCLUSIONS
Our results demonstrate that rats subject to OVX are unable to compensate for hypertrophy partly due to impaired Akt-endothelial nitric oxide synthase signaling along with deteriorated heart function and demonstrated increased mortality. In this review, we discussed the mechanisms of cardiac injury, which could play a critical role in postmenopausal hypertrophy, as well as the characteristics of the OVX-PO female rats as a model to test cardioprotective drugs in postmenopausal women.
Bhuiyan
Md Shenuarin
MS
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Fukunaga
Kohji
K
D000818:Animals; D004195:Disease Models, Animal; D004967:Estrogens / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000503:physiopathology; D006973:Hypertension; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000503:physiopathology*; D010052:Ovariectomy; D019869:Phosphatidylinositol 3-Kinases; D017698:Postmenopause / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D015398:Signal Transduction; D020257:Ventricular Remodeling / Q000502:physiology
D004967:Estrogens; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt