PMID- 33610040
OWN - NLM
STAT- MEDLINE
DCOM- 20210831
LR  - 20210831
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 547
DP  - 2021 Apr 2
TI  - Hyperhomocysteinemia-induced Nrf2/HO-1 pathway suppression aggravates cardiac 
      remodeling of hypertensive rats.
PG  - 125-130
LID - S0006-291X(21)00208-4 [pii]
LID - 10.1016/j.bbrc.2021.02.025 [doi]
AB  - ABJECTIVE: Interaction of hypertension and hyperhomocysteinemia (HHcy) leads to 
      enhanced cardiac remodeling in hypertensive heart disease. However, the mechanism 
      of collagen accumulation and cardiac remodeling remains unclear. In this study, 
      we attempted to evaluate the relationship between hypertension and HHcy in the 
      context of cardiac remodeling and to explore its mechanism of action. METHODS: 
      Wistar Kyoto (WKY) and spontaneous hypertension rats (SHR) were randomly divided 
      into four groups, namely WKY group, WKY + HHcy group, SHR group and SHR + HHcy 
      group. We measured blood pressure (BP), plasma homocysteine (Hcy), serum 
      superoxide dismutase (SOD) and serum malondialdehyde (MDA). We also examined 
      cardiac histopathology and gene and protein expression levels of Nrf2 and HO-1. 
      RESULTS: Compared with the WKY group, myocardial interstitial and perivascular 
      collagen deposition in the WKY + HHcy group, the SHR group and the SHR + HHcy 
      group increased successively, indicating that cardiac remodeling gradually 
      increased, and HHcy aggravated cardiac remodeling was more serious in 
      hypertensive rats. SOD decreased gradually in the four groups, while MDA was on 
      the contrary. WKY + HHcy and SHR + HHcy groups both suppressed Nrf2 and HO-1 
      expression and inhibited the translocation of Nrf2 from cytoplasm to nucleus 
      compared with their control groups, and the SHR + HHcy group had a stronger 
      inhibitory effect. CONCLUSION: HHcy enhanced cardiac remodeling in rats by 
      enhancing oxidative stress, suppressing the Nrf2/HO-1 pathway and Nrf2 nuclear 
      transport, and this inhibitory effect was stronger in the context of 
      hypertension.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Cao, Ping
AU  - Cao P
AD  - Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Cheeloo 
      College of Medicine, Shandong University, Jinan, Shandong, China; Department of 
      Geriatrics, Tai'an City Central Hospital, Taian, Shandong, China.
FAU - Zhang, Wangmeng
AU  - Zhang W
AD  - Department of Obstetrics, Tai'an City Central Hospital, Taian, Shandong, China.
FAU - Kong, Xue
AU  - Kong X
AD  - Department of Radiology, Tai'an City Central Hospital, Taian, Shandong, China.
FAU - Gao, Ning
AU  - Gao N
AD  - Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Cheeloo 
      College of Medicine, Shandong University, Jinan, Shandong, China.
FAU - Zhao, Xuan
AU  - Zhao X
AD  - Department of Cardiology, People's Hospital of Dongying, Dongying, Shandong, 
      China.
FAU - Xu, Rui
AU  - Xu R
AD  - Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Cheeloo 
      College of Medicine, Shandong University, Jinan, Shandong, China; Department of 
      Cardiology, The First Affiliated Hospital of Shandong First Medical University, 
      Jinan, Shandong, China. Electronic address: xuruicn@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210217
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, rat)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
RN  - EC 1.14.14.18 (Hmox1 protein, rat)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Heart Diseases/etiology/*metabolism/pathology
MH  - Heme Oxygenase (Decyclizing)/*metabolism
MH  - Hyperhomocysteinemia/*metabolism/pathology
MH  - Hypertension/*metabolism/pathology
MH  - Male
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Signal Transduction
MH  - *Ventricular Remodeling
OTO - NOTNLM
OT  - Cardiac remodeling
OT  - HHcy
OT  - HO-1
OT  - Hypertension
OT  - Nrf2
COIS- Declaration of competing interest The authors declare no conflict of interest.
EDAT- 2021/02/21 06:00
MHDA- 2021/09/01 06:00
CRDT- 2021/02/20 20:15
PHST- 2021/01/17 00:00 [received]
PHST- 2021/02/06 00:00 [accepted]
PHST- 2021/02/21 06:00 [pubmed]
PHST- 2021/09/01 06:00 [medline]
PHST- 2021/02/20 20:15 [entrez]
AID - S0006-291X(21)00208-4 [pii]
AID - 10.1016/j.bbrc.2021.02.025 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2021 Apr 2;547:125-130. doi: 
      10.1016/j.bbrc.2021.02.025. Epub 2021 Feb 17.