Loss of p27kip1 suppresses the myocardial senescence caused by estrogen deficiency

Estrogen deficiency accelerates the aging process and increases the risk of developing cardiovascular disease (CVD). Apoptosis is one of the important mechanisms of aging. p27(kip1) is a cyclin-dependent kinase inhibitor that can regulate cell cycle, apoptosis, and cell motility. p27(kip1) overexpression can inhibit cell cycle and increase apoptosis so it has been considered as a marker of aging. In the present study, bilateral ovariectomy (OVX) was performed as a model for menopause in wild-type (WT) and p27(kip1) knockout (KO) mice to assess the effects of p27(kip1) loss in myocardial aging caused by estrogen deficiency. We found that myocardial fibrosis and heart weight/body weight ratio of mice in the OVX group and p27(kip1) KO group were significantly increased. Echocardiography showed that the left ventricular diameter and volume of the WT OVX group increased significantly and the cardiac function decreased. However, there was no significant difference in the results of echocardiography between the two p27(kip1) KO groups. The aging and apoptosis indexes in OVX group were increased significantly, However, the indexes in p27(kip1) KO mice were decreased. The expression of antioxidant indexes in OVX group was decreased significantly and p27(kip1) KO can improve the antioxidant ability. These results provided that estrogen deficiency increased oxidative stress and apoptosis, accelerated aging of heart. p27(kip1) KO can partly delay the aging and apoptosis of heart through upregulated antioxidant enzymes.