PMID- 36046692
OWN - NLM
STAT- MEDLINE
DCOM- 20220907
LR  - 20220907
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2022
DP  - 2022
TI  - Hyperhomocysteinemia Promotes Cardiac Hypertrophy in Hypertension.
PG  - 1486157
LID - 10.1155/2022/1486157 [doi]
LID - 1486157
AB  - Hyperhomocysteinemia (HHcy) is positively linked with several cardiovascular 
      diseases; however, its role and underlying mechanisms in pathological cardiac 
      hypertrophy are still unclear. Here, we focused on the effects and underlying 
      mechanisms of HHcy in hypertensive cardiac hypertrophy, one of the most common 
      and typical types of pathological cardiac hypertrophy. By a retrospective 
      analysis of the association between HHcy and cardiac hypertrophy in a 
      hypertensive cohort, we found that the prevalence of HHcy was higher in patients 
      with hypertrophy and significantly associated with the presence of cardiac 
      hypertrophy after adjusting for other conventional risk factors. In mice, HHcy 
      induced by a methionine (2% wt/wt) diet feeding significantly promoted cardiac 
      hypertrophy as well as cardiac inflammation and fibrosis induced by 3-week 
      angiotensin capital I, Ukrainiancapital I, Ukrainian (Angcapital I, Ukrainiancapital I, Ukrainian) infusion (1000 ng/kg/min), while folic acid (0.006% wt/wt) 
      supplement corrected HHcy and attenuated AngII-stimulated cardiac phenotypes. 
      Mechanistic studies further showed that homocysteine (Hcy) exacerbated 
      AngII-stimulated expression of Calcineurin and nuclear factor of activated T 
      cells (NFAT), which could be attenuated by folic acid both in mice and in 
      neonatal rat cardiomyocytes. Moreover, treatment with cyclosporin A, an inhibitor 
      of Calcineurin, blocked Hcy-stimulated Calcineurin-NFAT signaling and hypertrophy 
      in neonatal rat cardiomyocytes. In conclusion, our study indicates that HHcy 
      promotes cardiac hypertrophy in hypertension, and Calcineurin-NFAT pathway might 
      be involved in the pro-hypertrophic effect of Hcy.
CI  - Copyright (c) 2022 Yawen Deng et al.
FAU - Deng, Yawen
AU  - Deng Y
AD  - Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical 
      University, Dalian, China.
FAU - Li, Zhitong
AU  - Li Z
AUID- ORCID: 0000-0002-1062-5878
AD  - Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical 
      University, Dalian, China.
FAU - An, Xiangbo
AU  - An X
AD  - Department of Interventional Therapy, First Affiliated Hospital of Dalian Medical 
      University, Dalian, China.
FAU - Fan, Rui
AU  - Fan R
AD  - Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical 
      University, Dalian, China.
FAU - Wang, Yao
AU  - Wang Y
AD  - Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical 
      University, Dalian, China.
FAU - Li, Jiatian
AU  - Li J
AD  - Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical 
      University, Dalian, China.
FAU - Yang, Xiaolei
AU  - Yang X
AUID- ORCID: 0000-0002-6132-5971
AD  - Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical 
      University, Dalian, China.
FAU - Liao, Jiawei
AU  - Liao J
AUID- ORCID: 0000-0001-7584-5225
AD  - Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical 
      University, Dalian, China.
FAU - Xia, Yunlong
AU  - Xia Y
AUID- ORCID: 0000-0001-7985-3273
AD  - Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical 
      University, Dalian, China.
LA  - eng
PT  - Journal Article
DEP - 20220822
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (NFATC Transcription Factors)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 935E97BOY8 (Folic Acid)
RN  - EC 3.1.3.16 (Calcineurin)
SB  - IM
MH  - Animals
MH  - Calcineurin/metabolism
MH  - Cardiomegaly/complications/metabolism
MH  - Folic Acid/pharmacology
MH  - Homocysteine/metabolism
MH  - Humans
MH  - *Hyperhomocysteinemia/complications/metabolism
MH  - *Hypertension/complications/metabolism
MH  - Mice
MH  - Myocytes, Cardiac/metabolism
MH  - NFATC Transcription Factors/metabolism
MH  - Rats
MH  - Retrospective Studies
PMC - PMC9423973
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2022/09/02 06:00
MHDA- 2022/09/08 06:00
PMCR- 2022/08/22
CRDT- 2022/09/01 02:34
PHST- 2022/06/08 00:00 [received]
PHST- 2022/08/03 00:00 [accepted]
PHST- 2022/09/01 02:34 [entrez]
PHST- 2022/09/02 06:00 [pubmed]
PHST- 2022/09/08 06:00 [medline]
PHST- 2022/08/22 00:00 [pmc-release]
AID - 10.1155/2022/1486157 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2022 Aug 22;2022:1486157. doi: 10.1155/2022/1486157. 
      eCollection 2022.