PMID- 22181043
OWN - NLM
STAT- MEDLINE
DCOM- 20120528
LR  - 20211021
IS  - 1744-4160 (Electronic)
IS  - 1381-3455 (Print)
IS  - 1381-3455 (Linking)
VI  - 118
IP  - 1
DP  - 2012 Feb
TI  - Mitochondrial mitophagic mechanisms of myocardial matrix metabolism and 
      remodelling.
PG  - 31-42
LID - 10.3109/13813455.2011.635660 [doi]
AB  - High levels of homocysteine (Hcy), known as hyperhomocysteinmia (HHcy), are 
      correlated with an increase in extracellular matrix remodelling (ECM) via the 
      matrix metalloproteinases (MMPs) and plasminogen/plasmin system. This results in 
      an increase deposition of collagen that leads to endothelial-myocyte (EM) and 
      myocyte-myocyte (MM) uncoupling; the physiological consequences are a plethora of 
      cardiovascular pathologies. Homocysteine-induced increase in intracellular and 
      mitochondrial Ca(2+) plays an important role in increasing reactive oxygen 
      species (ROS) within mitochondria and instigating mitophagy within the cell. This 
      occurs via several Hcy-mitigated processes: agonizing N-methyl-d-aspartate 
      receptor-1 (NMDA-R1), decreasing expression of peroxisome proliferator activator 
      receptor (PPAR) [thereby increasing oxidation], impairing Ca(2+) handling via 
      Na(+)/Ca(2+) exchanger (NCX1) and Sarco endoplasmic reticulum Ca(2+) ATPase 
      (SERCA-2a). The end result is an increase in ROS that directly or indirectly lead 
      to MMP activation within mitochondria or the cytoplasm. Hcy induces a 
      mitochondrial permeability transition that allows MMPs to be released from 
      mitochondria thereby metabolizing matrix and impairing cardiac function. Further 
      work remains to be elucidated concerning the specific mitochondrial mitophagic 
      mechanisms under which matrix metabolism and remodelling occurs. Moreover, the 
      therapeutic implications of NMDA and PPAR ligands are some promise to patient.
FAU - Vacek, Thomas P
AU  - Vacek TP
AD  - Department of Physiology and Biophysics, School of Medicine, University of 
      Louisville, Louisville, KY 40202, USA.
FAU - Vacek, Jonathan C
AU  - Vacek JC
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - R01 HL108621/HL/NHLBI NIH HHS/United States
GR  - R01 NS051568-05/NS/NINDS NIH HHS/United States
GR  - R01 HL071010/HL/NHLBI NIH HHS/United States
GR  - R01 NS051568/NS/NINDS NIH HHS/United States
GR  - R01 HL088012/HL/NHLBI NIH HHS/United States
GR  - R01 HL088012-04/HL/NHLBI NIH HHS/United States
GR  - NS-51568/NS/NINDS NIH HHS/United States
GR  - R01 HL074185-07/HL/NHLBI NIH HHS/United States
GR  - R01 HL108621-03/HL/NHLBI NIH HHS/United States
GR  - R01 HL108621-02/HL/NHLBI NIH HHS/United States
GR  - HL-71010/HL/NHLBI NIH HHS/United States
GR  - R01 HL074185/HL/NHLBI NIH HHS/United States
GR  - R01 HL071010-08/HL/NHLBI NIH HHS/United States
GR  - HL-74185/HL/NHLBI NIH HHS/United States
GR  - HL108621/HL/NHLBI NIH HHS/United States
GR  - HL-88012/HL/NHLBI NIH HHS/United States
GR  - R01 HL074185-09/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20111219
PL  - England
TA  - Arch Physiol Biochem
JT  - Archives of physiology and biochemistry
JID - 9510153
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Sodium-Calcium Exchanger)
RN  - 0 (sodium-calcium exchanger 1)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 9001-91-6 (Plasminogen)
RN  - EC 3.4.21.7 (Fibrinolysin)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Autophagy
MH  - Calcium/metabolism
MH  - Extracellular Matrix/*enzymology/metabolism/pathology
MH  - Fibrinolysin/metabolism
MH  - Homocysteine/*metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/*enzymology/pathology
MH  - Matrix Metalloproteinases/*metabolism
MH  - Mice
MH  - Mitochondria, Heart/*enzymology/metabolism/pathology
MH  - Myocardium/*enzymology/pathology
MH  - Myocytes, Cardiac/*enzymology/pathology
MH  - Oxidative Stress
MH  - Permeability
MH  - Peroxisome Proliferator-Activated Receptors/metabolism
MH  - Plasminogen/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism
MH  - Sodium-Calcium Exchanger/metabolism
MH  - Ventricular Remodeling
PMC - PMC3269507
MID - NIHMS346156
COIS- Declaration of interest The authors report no conflicts of interest. The authors 
      alone are responsible for the content and writing of this article.
EDAT- 2011/12/21 06:00
MHDA- 2012/05/29 06:00
PMCR- 2012/02/01
CRDT- 2011/12/21 06:00
PHST- 2011/12/21 06:00 [entrez]
PHST- 2011/12/21 06:00 [pubmed]
PHST- 2012/05/29 06:00 [medline]
PHST- 2012/02/01 00:00 [pmc-release]
AID - 10.3109/13813455.2011.635660 [doi]
PST - ppublish
SO  - Arch Physiol Biochem. 2012 Feb;118(1):31-42. doi: 10.3109/13813455.2011.635660. 
      Epub 2011 Dec 19.