The Coexistence of Hypertension and Ovariectomy Additively Increases Cardiac Apoptosis

Abstract

To investigate whether the coexistence of hypertension and ovariectomy will increase cardiac Fas receptor and mitochondrial-dependent apoptotic pathways, histopathological analysis, the TUNEL assay and Western blotting were performed on the excised hearts from three groups of female spontaneously hypertensive rats (SHR), which were divided into a sham-operated group (SHR-Sham), bilaterally ovariectomized group (SHR-OVX) and normotensive Wistar Kyoto rats (WKY). Compared with the WKY group, the SHR-Sham group exhibited decreased protein levels of ERα, ERβ, p-Akt/Akt, Bcl-2, Bcl-xL and p-Bad and decreased further in the SHR-OVX group, as well as protein levels of t-Bid, Bak, Bad, Bax, cytochrome c, activated caspase-9 and activated caspase-3 (mitochondria-dependent apoptosis) increased in the SHR-Sham group and increased further in the SHR-OVX group. Compared with the WKY group, protein levels of Fas ligand, TNF-α, Fas death receptors, TNFR1, FADD and activated caspase-8 (Fas receptor-dependent apoptosis) increased in the SHR-Sham group, but did not increase in the SHR-OVX group, except Fas ligand and TNF-α. The coexistence of hypertension and ovariectomy attenuated the estrogen receptor survival pathway and appeared to additively increase the cardiac mitochondria-dependent, but not the Fas receptor-dependent apoptosis pathway, which might provide one possible mechanism for the development of cardiac abnormalities in hypertensive postmenopausal women.

Cardiometabolic Changes in Different Gonadal Female States Caused by Mild Hyperuricemia and Exposure to a High-Fructose Diet

“…Hypertension causes pathological cardiac hypertrophy and is recognized as the most important predictor of cardiovascular morbidity and mortality, as well as an important risk factor for heart failure [ 25 ].…”

Combined effects of 17β-estradiol and exercise training on cardiac apoptosis in ovariectomized rats

“…Paraffin-embedded heart sections were cut into 2-μm thick. Hematoxylin-eosin staining was performed as previously reported [25]. In brief, the heart sections were de-paraffinized in xylene and rehydrated through graded alcohols (100%, 90%, 85% and 75%) and then rinsed in PBS (pH 7.2).…”

“…The heart sections were also stained with Masson’s trichrome stain kit (ScyTek Laboratories, Inc., UT, USA) as previously described [25]. Brief, the heart sections were incubated with Bouin solution at 60°C for 45 min, washed in running tap water until the yellow color disappeared.…”

Cardiovascular Benefits of Exercise Training in Postmenopausal Hypertension

“…Pathologic growth in heart wall thickness and volume is associated with cell death (apoptosis or necrosis) and often progresses to severe cardiac remodeling and heart failure leading to functional decompensation, whereas physiologic growth is associated with a normal or increased cardiac function [ 39 ]. Recent studies have reported that cardiac abnormalities in ovariectomized hypertensive rats have demonstrated increased cardiomyocyte hypertrophy, myocardial interstitial space, and reparative fibrosis, and more cardiomyocyte apoptosis [ 16 , 42 ].…”