PMID- 24585779
OWN - NLM
STAT- MEDLINE
DCOM- 20140615
LR  - 20211021
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 306
IP  - 8
DP  - 2014 Apr 15
TI  - Hyperhomocysteinemia attenuates angiogenesis through reduction of HIF-1alpha and 
      PGC-1alpha levels in muscle fibers during hindlimb ischemia.
PG  - H1116-27
LID - 10.1152/ajpheart.00003.2014 [doi]
AB  - Hyperhomocysteinemia (HHcy) is associated with elderly frailty, skeletal muscle 
      injury and malfunction, reduced vascular integrity and function, and mortality. 
      Although HHcy has been implicated in the impairment of angiogenesis after 
      hindlimb ischemia in murine models, the underlying mechanisms are still unclear. 
      We hypothesized that HHcy compromises skeletal muscle perfusion, collateral 
      formation, and arteriogenesis by diminishing postischemic vasculogenic responses 
      in muscle fibers. To test this hypothesis, we created femoral artery ligation in 
      wild-type and heterozygous cystathionine beta-synthase (CBS(+/-)) mice (a model for 
      HHcy) and assessed tissue perfusion, collateral vessel formation, and skeletal 
      muscle function using laser-Doppler perfusion imaging, barium angiography, and 
      fatigue tests. In addition, we assessed postischemic levels of VEGF and levels of 
      its muscle-specific regulators: hypoxia-inducible factor (HIF)-1alpha and peroxisome 
      proliferator-activated receptor-gamma coactivator (PGC)-1alpha. The observations 
      indicated dysregulation of VEGF, HIF-1alpha, and PGC-1alpha levels in ischemic skeletal 
      muscles of CBS(+/-) mice. Concomitant with the reduced ischemic angiogenic 
      responses, we also observed diminished leptin expression and attenuated Akt 
      signaling in ischemic muscle fibers of CBS(+/-) mice. Moreover, there was 
      enhanced atrogene, ubiquitin ligases that conjugate proteins for degradation 
      during muscle atrophy, transcription, and reduced muscle function after ischemia 
      in CBS(+/-) mice. These results suggest that HHcy adversely affects 
      muscle-specific ischemic responses and contributes to muscle frailty.
FAU - Veeranki, Sudhakar
AU  - Veeranki S
AD  - Department of Physiology and Biophysics, University of Louisville, Louisville, 
      Kentucky.
FAU - Givvimani, Srikanth
AU  - Givvimani S
FAU - Pushpakumar, Sathnur
AU  - Pushpakumar S
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - HL-108621/HL/NHLBI NIH HHS/United States
GR  - HL-74185/HL/NHLBI NIH HHS/United States
GR  - NS-84823/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140228
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Muscle Proteins)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (Tripartite Motif Proteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.3.2.27 (Fbxo32 protein, mouse)
RN  - EC 2.3.2.27 (SKP Cullin F-Box Protein Ligases)
RN  - EC 2.3.2.27 (Trim63 protein, mouse)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Animals
MH  - Behavior, Animal
MH  - Cystathionine beta-Synthase/deficiency/genetics
MH  - Femoral Artery/surgery
MH  - Gene Expression
MH  - Hindlimb/*blood supply
MH  - Hyperhomocysteinemia/*physiopathology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Ischemia/*physiopathology
MH  - Ligation
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Muscle Proteins/genetics
MH  - Muscle, Skeletal/blood supply/chemistry
MH  - Neovascularization, Physiologic/*physiology
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - SKP Cullin F-Box Protein Ligases/genetics
MH  - Swimming
MH  - Transcription Factors/*metabolism
MH  - Tripartite Motif Proteins
MH  - Ubiquitin-Protein Ligases/genetics
MH  - Vascular Endothelial Growth Factor A
PMC - PMC3989752
OTO - NOTNLM
OT  - Akt
OT  - CD31
OT  - angiogenesis
OT  - atrogin-1
OT  - hyperhomocysteinemia
OT  - hypoxia-inducible factor
OT  - ischemia
OT  - leptin
OT  - muscle ring finger-1
OT  - peroxisome proliferator-activated receptor-gamma coactivator-1alpha
OT  - skeletal muscle
OT  - vascular endothelial growth factor
EDAT- 2014/03/04 06:00
MHDA- 2014/06/16 06:00
PMCR- 2015/04/15
CRDT- 2014/03/04 06:00
PHST- 2014/03/04 06:00 [entrez]
PHST- 2014/03/04 06:00 [pubmed]
PHST- 2014/06/16 06:00 [medline]
PHST- 2015/04/15 00:00 [pmc-release]
AID - ajpheart.00003.2014 [pii]
AID - H-00003-2014 [pii]
AID - 10.1152/ajpheart.00003.2014 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2014 Apr 15;306(8):H1116-27. doi: 
      10.1152/ajpheart.00003.2014. Epub 2014 Feb 28.