PMID- 31178749
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201105
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 10
DP  - 2019
TI  - Hydrogen Sulfide Ameliorates Homocysteine-Induced Cardiac Remodeling and 
      Dysfunction.
PG  - 598
LID - 10.3389/fphys.2019.00598 [doi]
LID - 598
AB  - Patients with diabetes, a methionine-rich meat diet, or certain genetic 
      polymorphisms show elevated levels of homocysteine (Hcy), which is strongly 
      associated with the development of cardiovascular disease including diabetic 
      cardiomyopathy. However, reducing Hcy levels with folate shows no beneficial 
      cardiac effects. We have previously shown that a hydrogen sulfide (H(2)S), a 
      by-product of Hcy through transsulfuration by cystathionine beta synthase (CBS), 
      donor mitigates Hcy-induced hypertrophy in cardiomyocytes. However, the in vivo 
      cardiac effects of H(2)S in the context of hyperhomocysteinemia (HHcy) have not 
      been studied. We tested the hypothesis that HHcy causes cardiac remodeling and 
      dysfunction in vivo, which is ameliorated by H(2)S. Twelve-week-old male CBS(+/-) 
      (a model of HHcy) and sibling CBS(+/+) (WT) mice were treated with SG1002 (a slow 
      release H(2)S donor) diet for 4 months. The left ventricle of CBS(+/-) mice 
      showed increased expression of early remodeling signals c-Jun and c-Fos, 
      increased interstitial collagen deposition, and increased cellular hypertrophy. 
      Notably, SG1002 treatment slightly reduced c-Jun and c-Fos expression, decreased 
      interstitial fibrosis, and reduced cellular hypertrophy. Pressure volume loop 
      analyses in CBS(+/-) mice revealed increased end systolic pressure with no change 
      in stroke volume (SV) suggesting increased afterload, which was abolished by 
      SG1002 treatment. Additionally, SG1002 treatment increased end-diastolic volume 
      and SV in CBS(+/-) mice, suggesting increased ventricular filling. These results 
      demonstrate SG1002 treatment alleviates cardiac remodeling and afterload in HHcy 
      mice. H(2)S may be cardioprotective in conditions where H(2)S is reduced and Hcy 
      is elevated.
FAU - Kar, Sumit
AU  - Kar S
AD  - Department of Cellular and Integrative Physiology, University of Nebraska Medical 
      Center, Omaha, NE, United States.
FAU - Shahshahan, Hamid R
AU  - Shahshahan HR
AD  - Department of Cellular and Integrative Physiology, University of Nebraska Medical 
      Center, Omaha, NE, United States.
FAU - Kambis, Tyler N
AU  - Kambis TN
AD  - Department of Cellular and Integrative Physiology, University of Nebraska Medical 
      Center, Omaha, NE, United States.
FAU - Yadav, Santosh K
AU  - Yadav SK
AD  - Department of Cellular and Integrative Physiology, University of Nebraska Medical 
      Center, Omaha, NE, United States.
FAU - Li, Zhen
AU  - Li Z
AD  - Department of Pharmacology and Experimental Therapeutics, Cardiovascular Center 
      of Excellence, Louisiana State University Health Sciences Center, New Orleans, 
      LA, United States.
FAU - Lefer, David J
AU  - Lefer DJ
AD  - Department of Pharmacology and Experimental Therapeutics, Cardiovascular Center 
      of Excellence, Louisiana State University Health Sciences Center, New Orleans, 
      LA, United States.
FAU - Mishra, Paras K
AU  - Mishra PK
AD  - Department of Cellular and Integrative Physiology, University of Nebraska Medical 
      Center, Omaha, NE, United States.
AD  - Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE, 
      United States.
LA  - eng
GR  - R01 HL113281/HL/NHLBI NIH HHS/United States
GR  - R01 HL116205/HL/NHLBI NIH HHS/United States
GR  - R01 HL146098/HL/NHLBI NIH HHS/United States
GR  - U54 GM104940/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20190524
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC6544124
OTO - NOTNLM
OT  - H2S
OT  - cardioprotection
OT  - fibrosis
OT  - hyperhomocysteinemia
OT  - hypertrophy
EDAT- 2019/06/11 06:00
MHDA- 2019/06/11 06:01
PMCR- 2019/05/24
CRDT- 2019/06/11 06:00
PHST- 2019/03/18 00:00 [received]
PHST- 2019/04/26 00:00 [accepted]
PHST- 2019/06/11 06:00 [entrez]
PHST- 2019/06/11 06:00 [pubmed]
PHST- 2019/06/11 06:01 [medline]
PHST- 2019/05/24 00:00 [pmc-release]
AID - 10.3389/fphys.2019.00598 [doi]
PST - epublish
SO  - Front Physiol. 2019 May 24;10:598. doi: 10.3389/fphys.2019.00598. eCollection 
      2019.