PMID- 24771691
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140428
LR  - 20211021
IS  - 2051-817X (Print)
IS  - 2051-817X (Electronic)
IS  - 2051-817X (Linking)
VI  - 2
IP  - 4
DP  - 2014
TI  - Mitochondrial mitophagy in mesenteric artery remodeling in hyperhomocysteinemia.
PG  - e00283
LID - 10.14814/phy2.283 [doi]
LID - e00283
AB  - Abstract Although high levels of homocysteine also termed as hyperhomocysteinemia 
      (HHcy) has been associated with inflammatory bowel disease and mesenteric artery 
      occlusion, the mitochondrial mechanisms behind endothelial dysfunction that lead 
      to mesenteric artery remodeling are largely unknown. We hypothesize that in HHcy 
      there is increased mitochondrial fission due to altered Mfn-2/Drp-1 ratio, which 
      leads to endothelial dysfunction and collagen deposition in the mesenteric artery 
      inducing vascular remodeling. To test this hypothesis, we used four groups of 
      mice: (i) WT (C57BL/6J); (ii) mice with HHcy (CBS+/-); (iii) oxidative stress 
      resistant mice (C3H) and (iv) mice with HHcy and oxidative stress resistance 
      (CBS+/-/C3H). For mitochondrial dynamics, we studied the expression of Mfn-2 
      which is a mitochondrial fusion protein and Drp-1 which is a mitochondrial 
      fission protein by western blots, real-time PCR and immunohistochemistry. We also 
      examined oxidative stress markers, endothelial cell, and gap junction proteins 
      that play an important role in endothelial dysfunction. Our data showed increase 
      in oxidative stress, mitochondrial fission (Drp-1), and collagen deposition in 
      CBS+/- compared to WT and C3H mice. We also observed significant down regulation 
      of Mfn-2 (mitochondrial fusion marker), CD31, eNOS and connexin 40 (gap junction 
      protein) in CBS+/- mice as compared to WT and C3H mice. In conclusion, our data 
      suggested that HHcy increased mitochondrial fission (i.e., decreased Mfn-2/Drp-1 
      ratio, causing mitophagy) that leads to endothelial cell damage and collagen 
      deposition in the mesenteric artery. This is a novel report on the role of 
      mitochondrial dynamics alteration defining mesenteric artery remodeling.
FAU - Familtseva, Anastasia
AU  - Familtseva A
AD  - Department of Physiology and Biophysics, School of Medicine, University of 
      Louisville, Louisville, 40202, Kentucky.
FAU - Kalani, Anuradha
AU  - Kalani A
FAU - Chaturvedi, Pankaj
AU  - Chaturvedi P
FAU - Tyagi, Neetu
AU  - Tyagi N
FAU - Metreveli, Naira
AU  - Metreveli N
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
PT  - Journal Article
DEP - 20140422
PL  - United States
TA  - Physiol Rep
JT  - Physiological reports
JID - 101607800
PMC - PMC4001876
OTO - NOTNLM
OT  - Endothelial dysfunction
OT  - hyperhomocysteinemia
OT  - mitochondrial dynamics
OT  - oxidative stress
EDAT- 2014/04/29 06:00
MHDA- 2014/04/29 06:01
PMCR- 2014/04/23
CRDT- 2014/04/29 06:00
PHST- 2014/04/29 06:00 [entrez]
PHST- 2014/04/29 06:00 [pubmed]
PHST- 2014/04/29 06:01 [medline]
PHST- 2014/04/23 00:00 [pmc-release]
AID - 2/4/e00283 [pii]
AID - phy2283 [pii]
AID - 10.14814/phy2.283 [doi]
PST - epublish
SO  - Physiol Rep. 2014 Apr 22;2(4):e00283. doi: 10.14814/phy2.283. Print 2014.