PMID- 33994505
OWN - NLM
STAT- MEDLINE
DCOM- 20210610
LR  - 20240226
IS  - 1349-3299 (Electronic)
IS  - 1349-2365 (Linking)
VI  - 62
IP  - 3
DP  - 2021 May 29
TI  - Low Dose of Folic Acid Can Ameliorate Hyperhomocysteinemia-Induced Cardiac 
      Fibrosis and Diastolic Dysfunction in Spontaneously Hypertensive Rats.
PG  - 627-635
LID - 10.1536/ihj.20-593 [doi]
AB  - To evaluate whether lowering plasma homocysteine (Hcy) levels at different doses 
      of folic acid (FA) could reduce cardiac fibrosis and diastolic dysfunction in 
      spontaneously hypertensive rats (SHRs) with hyperhomocysteinemia (Hhcy) and 
      investigate the possible mechanism of action.We randomly divided 32 male SHRs 
      into control, Hhcy, Hhcy + low-dose FA (LFA), and Hhcy + high-dose FA (HFA) 
      groups. Echocardiography and Masson staining of cardiac tissue were used to 
      assess diastolic function and cardiac fibrosis. Blood pressure (BP) and Hcy 
      levels were measured during the experiment. We also measured the indicators of 
      oxidative stress (OS) and examined the expression of nuclear factor erythroid 
      2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes and proteins using 
      real-time polymerase chain reaction (PCR), immunohistochemistry, and western 
      blotting to explore the possible mechanism of action.FA treatment reversed SHR 
      cardiomyocyte interstitial and perivascular collagen deposition and diastolic 
      dysfunction exacerbated by Hhcy. These effects were associated with promoting the 
      translocation of Nrf2 from the cytoplasm to the nucleus, activating HO-1 
      expression and inhibiting OS. However, HFA did not show any additional benefit 
      from LFA in reducing cardiac injury.Even at a low dose, FA can ameliorate 
      Hhcy-induced cardiac fibrosis and diastolic dysfunction in SHRs by activating 
      Nrf2/HO-1 pathway and inhibiting OS, independent of BP, providing evidence for 
      the efficacy of LFA in the treatment of hypertension associated with Hhcy.
FAU - Cao, Ping
AU  - Cao P
AD  - Department of Cardiology, Shandong Qianfoshan Hospital, Cheeloo College of 
      Medicine, Shandong University.
AD  - Department of Geriatrics, Taian City Central Hospital.
FAU - Zhang, Wangmeng
AU  - Zhang W
AD  - Department of Geriatrics, Taian City Central Hospital.
FAU - Wang, Guicheng
AU  - Wang G
AD  - Department of Geriatrics, Taian City Central Hospital.
FAU - Zhao, Xuan
AU  - Zhao X
AD  - Department of Cardiology, People's Hospital of Dongying.
FAU - Gao, Ning
AU  - Gao N
AD  - Department of Cardiology, Shandong Qianfoshan Hospital, Cheeloo College of 
      Medicine, Shandong University.
FAU - Liu, Zhen
AU  - Liu Z
AD  - Department of Geriatrics, Taian City Central Hospital.
FAU - Xu, Rui
AU  - Xu R
AD  - Department of Cardiology, Shandong Qianfoshan Hospital, Cheeloo College of 
      Medicine, Shandong University.
AD  - Department of Cardiology, The First Affiliated Hospital of Shandong First Medical 
      University.
LA  - eng
PT  - Journal Article
DEP - 20210515
PL  - Japan
TA  - Int Heart J
JT  - International heart journal
JID - 101244240
RN  - 0 (Hematinics)
RN  - 935E97BOY8 (Folic Acid)
SB  - IM
MH  - Animals
MH  - Diastole
MH  - Drug Evaluation, Preclinical
MH  - Fibrosis
MH  - Folic Acid/*therapeutic use
MH  - Heart/physiopathology
MH  - Heart Diseases/pathology/physiopathology/*prevention & control
MH  - Hematinics/*therapeutic use
MH  - Hyperhomocysteinemia/*complications
MH  - Hypertension/*complications
MH  - Male
MH  - Myocardium/pathology
MH  - Random Allocation
MH  - Rats, Inbred SHR
MH  - Rats
OTO - NOTNLM
OT  - Hhcy
OT  - Hypertension
OT  - Nrf2/HO-1 pathway
EDAT- 2021/05/18 06:00
MHDA- 2021/06/11 06:00
CRDT- 2021/05/17 05:53
PHST- 2021/05/18 06:00 [pubmed]
PHST- 2021/06/11 06:00 [medline]
PHST- 2021/05/17 05:53 [entrez]
AID - 10.1536/ihj.20-593 [doi]
PST - ppublish
SO  - Int Heart J. 2021 May 29;62(3):627-635. doi: 10.1536/ihj.20-593. Epub 2021 May 
      15.