TY - JOUR
T1 - The coexistence of hypertension and ovariectomy additively increases cardiac apoptosis
AU - Lin, Yi Yuan
AU - Cheng, Yu Jung
AU - Hu, Jun
AU - Chu, Li Xi
AU - Shyu, Woei Cherng
AU - Kao, Chung Lan
AU - Lin, Tzer Bin
AU - Kuo, Chia Hua
AU - Yang, Ai Lun
AU - Lee, Shin Da
N1 - Funding Information:
This study was supported by the National Science Council (NSC95-2314-B-006-073-MY2, MOST103-2314-B-039-005 and MOST101-2410-H-845-015-MY3), China Medical University and Asia University (CMU99-ASIA-04), Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019) and University of Taipei, Taiwan. Research was supported by The Program for Professor of Special Appointment (Eastern Scholar, Honorary Chair Professor) at Shanghai Institute of Higher Education (No. 2012-47). We would like to thank Michael Burton, Asia University, for proof-reading the manuscript.
Publisher Copyright:
© 2016 by the authors; licensee MDPI, Basel, Switzerland.
PY - 2016/12/6
Y1 - 2016/12/6
N2 - To investigate whether the coexistence of hypertension and ovariectomy will increase cardiac Fas receptor and mitochondrial-dependent apoptotic pathways, histopathological analysis, the TUNEL assay andWestern 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 ER_, ER_, 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-_, 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-_. 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.
AB - To investigate whether the coexistence of hypertension and ovariectomy will increase cardiac Fas receptor and mitochondrial-dependent apoptotic pathways, histopathological analysis, the TUNEL assay andWestern 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 ER_, ER_, 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-_, 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-_. 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.
KW - Caspase
KW - Cell death
KW - Heart
KW - Menopausal hypertension
UR - http://www.scopus.com/inward/record.url?scp=85004091916&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85004091916&partnerID=8YFLogxK
U2 - 10.3390/ijms17122036
DO - 10.3390/ijms17122036
M3 - Article
C2 - 27929425
AN - SCOPUS:85004091916
VL - 17
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 12
M1 - 2036
ER -