PMID- 24033327
OWN - NLM
STAT- MEDLINE
DCOM- 20140929
LR  - 20220223
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 38
IP  - 2
DP  - 2014 Feb
TI  - Alcohol modulation of cardiac matrix metalloproteinases (MMPs) and tissue 
      inhibitors of MMPs favors collagen accumulation.
PG  - 448-56
LID - 10.1111/acer.12239 [doi]
AB  - BACKGROUND: Chronic alcohol consumption has been shown in human and animal 
      studies to result in collagen accumulation, myocardial fibrosis, and heart 
      failure. Cardiac fibroblasts produce collagen and regulate extracellular matrix 
      (ECM) homeostasis through the synthesis and activity of matrix metalloproteinases 
      (MMPs) and tissue inhibitors of MMPs (TIMPs), with the balance of MMPs/TIMPs 
      determining the rate of collagen turnover. Dynamic changes of MMP and TIMP 
      expression were reported in alcohol-induced hepatic fibrosis; however, the effect 
      of alcohol on MMP/TIMP balance in the heart and cardiac fibroblasts is unknown. 
      We hypothesized that alcohol exposure alters cardiac fibroblast MMP and TIMP 
      expression to promote collagen accumulation in the heart. METHODS: Cardiac 
      fibroblasts isolated from adult rats were cultured in the presence of alcohol 
      (12.5 to 200 mM) for 48 hours. MMP, TIMP, and collagen type I and III expression 
      were assayed by Western blot analysis. Hydroxyproline (HPro) was used as a marker 
      of collagen production. The in vivo cardiac effects of ethanol (EtOH) were 
      determined using rats exposed to EtOH vapor for 2 weeks, resulting in blood 
      alcohol levels of 150 to 200 mg/dl. Cardiac collagen volume fraction (CVF), as 
      well as MMP, TIMP, and collagen expression, was assessed. RESULTS: EtOH-exposed 
      rats exhibited up-regulation of TIMP-1, TIMP-3 and TIMP-4 in the heart, with no 
      significant increases in MMPs. Cardiac fibroblasts exhibited transformation to a 
      profibrotic phenotype following exposure to alcohol. These changes were reflected 
      by increased alpha-smooth muscle actin and collagen I and III expression, as well as 
      increased collagen secretion. In vivo EtOH exposure also produced fibrosis, 
      indicated by increased CVF and expression of collagens. CONCLUSIONS: Alcohol 
      exposure modulates cardiac fibroblast MMP/TIMP expression favoring a profile 
      associated with collagen accumulation. Our data suggest that this disrupted 
      MMP/TIMP profile may contribute to the development of myocardial fibrosis and 
      cardiac dysfunction resulting from chronic alcohol abuse.
CI  - Copyright (c) 2013 by the Research Society on Alcoholism.
FAU - El Hajj, Elia C
AU  - El Hajj EC
AD  - Department of Physiology , School of Medicine, Louisiana State University Health 
      Science Center, New Orleans, Louisiana.
FAU - El Hajj, Milad C
AU  - El Hajj MC
FAU - Voloshenyuk, Tetyana G
AU  - Voloshenyuk TG
FAU - Mouton, Alan J
AU  - Mouton AJ
FAU - Khoutorova, Elena
AU  - Khoutorova E
FAU - Molina, Patricia E
AU  - Molina PE
FAU - Gilpin, Nicholas W
AU  - Gilpin NW
FAU - Gardner, Jason D
AU  - Gardner JD
LA  - eng
GR  - P60 AA009803/AA/NIAAA NIH HHS/United States
GR  - P20 RR016456/RR/NCRR NIH HHS/United States
GR  - 5P60AA09803-19/AA/NIAAA NIH HHS/United States
GR  - P20RR016456/RR/NCRR NIH HHS/United States
GR  - R25 AA021304/AA/NIAAA NIH HHS/United States
GR  - P20 RR018766/RR/NCRR NIH HHS/United States
GR  - R00AA018400/AA/NIAAA NIH HHS/United States
GR  - R00 AA018400/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130819
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Actins)
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 0 (smooth muscle actin, rat)
RN  - 3K9958V90M (Ethanol)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - RMB44WO89X (Hydroxyproline)
SB  - IM
MH  - Actins/metabolism
MH  - Alcoholism/enzymology/pathology
MH  - Animals
MH  - Blotting, Western
MH  - Central Nervous System Depressants/*pharmacology
MH  - Collagen/*metabolism
MH  - Ethanol/*pharmacology
MH  - Fibroblasts/drug effects/enzymology/metabolism
MH  - Fibrosis
MH  - Heart/*drug effects
MH  - Hydroxyproline/metabolism
MH  - Male
MH  - Matrix Metalloproteinases/*metabolism
MH  - Myocardium/*enzymology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tissue Inhibitor of Metalloproteinases/*metabolism
PMC - PMC4080812
MID - NIHMS510076
OTO - NOTNLM
OT  - Ethanol
OT  - Extracellular Matrix Remodeling
OT  - Fibrosis
OT  - Heart
OT  - Proteinase
EDAT- 2013/09/17 06:00
MHDA- 2014/09/30 06:00
PMCR- 2015/02/01
CRDT- 2013/09/17 06:00
PHST- 2012/10/03 00:00 [received]
PHST- 2013/07/01 00:00 [accepted]
PHST- 2013/09/17 06:00 [entrez]
PHST- 2013/09/17 06:00 [pubmed]
PHST- 2014/09/30 06:00 [medline]
PHST- 2015/02/01 00:00 [pmc-release]
AID - 10.1111/acer.12239 [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2014 Feb;38(2):448-56. doi: 10.1111/acer.12239. Epub 2013 
      Aug 19.