Estrogen deprivation aggravates cardiac hypertrophy in nonobese Type 2 diabetic Goto-Kakizaki (GK) rats.
Both Type 2 diabetes mellitus (T2DM) and estrogen deprivation have been shown to be associated with the development of cardiovascular disease and adverse cardiac remodeling. However, the role of estrogen deprivation on adverse cardiac remodeling in nonobese T2DM rats has not been clearly elucidated. We hypothesized that estrogen-deprivation aggravates adverse cardiac remodeling in Goto-Kakizaki (GK) rats. Wild-type (WT) and GK rats at the age of 9 months old were divided into two subgroups to have either a sham operation (WTS, GKS) or a bilateral ovariectomy (WTO, GKO) (n = 6/subgroup). Four months after the operation, the rats were killed, and the heart was excised rapidly. Metabolic parameters, cardiomyocytes hypertrophy, cardiac fibrosis, and biochemical parameters were determined. GK rats had hyperglycemia with hypoinsulinemia, and estrogen deprivation did not increase the severity of T2DM. Cardiac hypertrophy, cardiac oxidative stress, and phosphor-antinuclear factor κB were higher in WTO and GKS rats than WTS rats, and they markedly increased in GKO rats compared with GKS rats. Furthermore, cardiac fibrosis, transforming growth factor-β, Bax, phosphor-p38, and peroxisome proliferator- activated receptor γ coactivator-1α expression were increased in GKS and GKO rats compared with the lean rats. However, mitochondrial dynamics proteins including dynamin-related protein 1 and mitofusin-2 were not altered by T2DM and estrogen deprivation. Although estrogen deprivation did not aggravate T2DM in GK rats, it increased the severity of cardiac hypertrophy by provoking cardiac inflammation and oxidative stress in nonobese GK rats.
['Apaijai|Nattayaporn|N|', 'Charoenphandhu|Narattaphol|N|', 'Ittichaichareon|Jitjiroj|J|', 'Suntornsaratoon|Panan|P|', 'Krishnamra|Nateetip|N|', 'Aeimlapa|Ratchaneevan|R|', 'Chattipakorn|Siriporn C|SC|', 'Chattipakorn|Nipon|N|']
D000818:Animals D015415:Biomarkers D006332:Cardiomegaly D003924:Diabetes Mellitus, Type 2 D004195:Disease Models, Animal D004967:Estrogens D005260:Female D006321:Heart D006943:Hyperglycemia D007249:Inflammation D008929:Mitochondria, Heart D010052:Ovariectomy D018384:Oxidative Stress D051381:Rats D017208:Rats, Wistar
cardiac hypertrophy Diabetes oxidative stress mitochondrial dysfunction