PMID- 18990685
OWN - NLM
STAT- MEDLINE
DCOM- 20090312
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 284
IP  - 3
DP  - 2009 Jan 16
TI  - Caloric restriction stimulates revascularization in response to ischemia via 
      adiponectin-mediated activation of endothelial nitric-oxide synthase.
PG  - 1718-24
LID - 10.1074/jbc.M805301200 [doi]
AB  - Caloric restriction (CR) can extend longevity and modulate the features of 
      obesity-related metabolic and vascular diseases. However, the functional roles of 
      CR in regulation of revascularization in response to ischemia have not been 
      examined. Here we investigated whether CR modulates vascular response by 
      employing a murine hindlimb ischemia model. Wild-type (WT) mice were randomly 
      divided into two groups that were fed either ad libitum (AL) or CR (65% of the 
      diet consumption of AL). Four weeks later, mice were subjected to unilateral 
      hindlimb ischemic surgery. Body weight of WT mice fed CR (CR-WT) was decreased by 
      26% compared with WT mice fed AL (AL-WT). Revascularization of ischemic hindlimb 
      relative to the contralateral limb was accelerated in CR-WT compared with AL-WT 
      as evaluated by laser Doppler blood flow and capillary density analyses. CR-WT 
      mice had significantly higher plasma levels of the fat-derived hormone 
      adiponectin compared with AL-WT mice. In contrast to WT mice, CR did not affect 
      the revascularization of ischemic limbs of adiponectin-deficient (APN-KO) mice. 
      CR stimulated the phosphorylation of endothelial nitric-oxide synthase (eNOS) in 
      the ischemic limbs of WT mice. CR increased plasma adiponectin levels in eNOS-KO 
      mice but did not stimulate limb perfusion in this strain. CR-WT mice showed 
      enhanced phosphorylation of AMP-activated protein kinase (AMPK) in ischemic 
      muscle, and administration of AMPK inhibitor compound C abolished CR-induced 
      increase in limb perfusion and eNOS phosphorylation in WT mice. Our observations 
      indicate that CR can promote revascularization in response to tissue ischemia via 
      an AMPK-eNOS-dependent mechanism that is mediated by adiponectin.
FAU - Kondo, Megumi
AU  - Kondo M
AD  - Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya 
      466-8550, Japan.
FAU - Shibata, Rei
AU  - Shibata R
FAU - Miura, Rie
AU  - Miura R
FAU - Shimano, Masayuki
AU  - Shimano M
FAU - Kondo, Kazuhisa
AU  - Kondo K
FAU - Li, Ping
AU  - Li P
FAU - Ohashi, Taiki
AU  - Ohashi T
FAU - Kihara, Shinji
AU  - Kihara S
FAU - Maeda, Norikazu
AU  - Maeda N
FAU - Walsh, Kenneth
AU  - Walsh K
FAU - Ouchi, Noriyuki
AU  - Ouchi N
FAU - Murohara, Toyoaki
AU  - Murohara T
LA  - eng
GR  - R01 HL091949-02/HL/NHLBI NIH HHS/United States
GR  - R01 HL091949/HL/NHLBI NIH HHS/United States
GR  - R01 HL086785/HL/NHLBI NIH HHS/United States
GR  - P01 HL081587-040003/HL/NHLBI NIH HHS/United States
GR  - R01 HL086785-19/HL/NHLBI NIH HHS/United States
GR  - HL81587/HL/NHLBI NIH HHS/United States
GR  - P01 HL081587/HL/NHLBI NIH HHS/United States
GR  - HL86785/HL/NHLBI NIH HHS/United States
GR  - HL91949/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20081106
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adiponectin)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
RN  - 10K52CIC1Z (dorsomorphin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, mouse)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Adiponectin/*blood
MH  - Animals
MH  - *Caloric Restriction
MH  - Hindlimb/blood supply/metabolism
MH  - Ischemia/*blood
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle, Skeletal/blood supply/*metabolism
MH  - *Neovascularization, Physiologic
MH  - Nitric Oxide Synthase Type III/*metabolism
MH  - Phosphorylation
MH  - Pyrazoles/pharmacology
MH  - Pyrimidines/pharmacology
PMC - PMC2615500
EDAT- 2008/11/08 09:00
MHDA- 2009/03/13 09:00
PMCR- 2010/01/16
CRDT- 2008/11/08 09:00
PHST- 2008/11/08 09:00 [pubmed]
PHST- 2009/03/13 09:00 [medline]
PHST- 2008/11/08 09:00 [entrez]
PHST- 2010/01/16 00:00 [pmc-release]
AID - S0021-9258(19)82189-0 [pii]
AID - 1718 [pii]
AID - 10.1074/jbc.M805301200 [doi]
PST - ppublish
SO  - J Biol Chem. 2009 Jan 16;284(3):1718-24. doi: 10.1074/jbc.M805301200. Epub 2008 
      Nov 6.