PMID- 19737384
OWN - NLM
STAT- MEDLINE
DCOM- 20091228
LR  - 20211020
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 8
DP  - 2009 Sep 8
TI  - Pioglitazone enhances collateral blood flow in ischemic hindlimb of diabetic mice 
      through an Akt-dependent VEGF-mediated mechanism, regardless of PPARgamma 
      stimulation.
PG  - 49
LID - 10.1186/1475-2840-8-49 [doi]
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is commonly associated with both 
      microvascular and macrovascular complications and a strong correlation exists 
      between glycaemic control and the incidence and progression of vascular 
      complications. Pioglitazone, a Peroxisome proliferator-activated receptor-gamma 
      (PPARgamma) ligand indicated for therapy of type T2DM, induces vascular effects 
      that seem to occur independently of glucose lowering. METHODS: By using a 
      hindlimb ischemia murine model, in this study we have found that pioglitazone 
      restores the blood flow recovery and capillary density in ischemic muscle of 
      diabetic mice and that this process is associated with increased expression of 
      Vascular Endothelial Growth Factor (VEGF). Importantly, these beneficial effects 
      are abrogated when endogenous Akt is inhibited; furthermore, the direct 
      activation of PPARgamma, with its selective agonist GW1929, does not restore 
      blood flow recovery and capillary density. Finally, an important collateral 
      vessel growth is obtained with combined treatment with pioglitazone and selective 
      PPARgamma inhibitor GW9662. CONCLUSION: These data demonstrate that Akt-VEGF 
      pathway is essential for ischemia-induced angiogenic effect of pioglitazone and 
      that pioglitazone exerts this effect via a PPARgamma independent manner.
FAU - Biscetti, Federico
AU  - Biscetti F
AD  - Laboratory of Vascular Biology and Genetics, Department of Medicine, A Gemelli 
      University Hospital, Catholic University School of Medicine, Rome, Italy. 
      f.biscetti@gmail.com
FAU - Straface, Giuseppe
AU  - Straface G
FAU - Arena, Vincenzo
AU  - Arena V
FAU - Stigliano, Egidio
AU  - Stigliano E
FAU - Pecorini, Giovanni
AU  - Pecorini G
FAU - Rizzo, Paola
AU  - Rizzo P
FAU - De Angelis, Giulia
AU  - De Angelis G
FAU - Iuliano, Luigi
AU  - Iuliano L
FAU - Ghirlanda, Giovanni
AU  - Ghirlanda G
FAU - Flex, Andrea
AU  - Flex A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090908
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (2-chloro-5-nitrobenzanilide)
RN  - 0 (Anilides)
RN  - 0 (Benzophenones)
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (PPAR gamma)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, mouse)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - X4OV71U42S (Pioglitazone)
RN  - X8S066WKF4 (GW 1929)
SB  - IM
MH  - Anilides/pharmacology
MH  - Animals
MH  - Benzophenones/pharmacology
MH  - Blood Flow Velocity/drug effects
MH  - Blood Glucose/analysis
MH  - Collateral Circulation/*drug effects
MH  - Diabetes Mellitus, Experimental/drug therapy/physiopathology
MH  - Hindlimb/*blood supply/pathology
MH  - Hypoglycemic Agents/pharmacology/therapeutic use
MH  - Ischemia/*drug therapy/physiopathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oncogene Protein v-akt/*physiology
MH  - PPAR gamma/*agonists/antagonists & inhibitors
MH  - Pioglitazone
MH  - Signal Transduction/drug effects
MH  - Thiazolidinediones/*pharmacology/therapeutic use
MH  - Tyrosine/analogs & derivatives/pharmacology
MH  - Up-Regulation/drug effects
MH  - Vascular Endothelial Growth Factor A/biosynthesis/genetics/*physiology
PMC - PMC2745363
EDAT- 2009/09/10 06:00
MHDA- 2009/12/29 06:00
PMCR- 2009/09/08
CRDT- 2009/09/10 06:00
PHST- 2009/07/29 00:00 [received]
PHST- 2009/09/08 00:00 [accepted]
PHST- 2009/09/10 06:00 [entrez]
PHST- 2009/09/10 06:00 [pubmed]
PHST- 2009/12/29 06:00 [medline]
PHST- 2009/09/08 00:00 [pmc-release]
AID - 1475-2840-8-49 [pii]
AID - 10.1186/1475-2840-8-49 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2009 Sep 8;8:49. doi: 10.1186/1475-2840-8-49.