Loss of p27kip1 suppresses the myocardial senescence caused by estrogen deficiency.

Abstract

Estrogen deficiency accelerates the aging process and increases the risk of developing cardiovascular disease (CVD). Apoptosis is one of the important mechanisms of aging. p27kip1 is a cyclin-dependent kinase inhibitor that can regulate cell cycle, apoptosis, and cell motility. p27kip1 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 p27kip1 knockout (KO) mice to assess the effects of p27kip1 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 p27kip1 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 p27kip1 KO groups. The aging and apoptosis indexes in OVX group were increased significantly, However, the indexes in p27kip1 KO mice were decreased. The expression of antioxidant indexes in OVX group was decreased significantly and p27kip1 KO can improve the antioxidant ability. These results provided that estrogen deficiency increased oxidative stress and apoptosis, accelerated aging of heart. p27kip1 KO can partly delay the aging and apoptosis of heart through upregulated antioxidant enzymes.