PMID- 15485696
OWN - NLM
STAT- MEDLINE
DCOM- 20050110
LR  - 20131121
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 64
IP  - 2
DP  - 2004 Nov 1
TI  - Differential effects of MCP-1 and leptin on collateral flow and arteriogenesis.
PG  - 356-64
AB  - OBJECTIVE: Strategies to therapeutically stimulate collateral artery growth in 
      experimental models have been studied intensively in the last decades. However, 
      the experimental methods to detect collateral artery growth are discussed 
      controversially and vary significantly. We compared different methods in a model 
      of arteriogenesis in the rabbit hind limb and determined the effects on 
      collateral flow of a known pro-arteriogenic factor, monocyte chemoattractant 
      protein-1 (MCP-1), and a cytokine not previously evaluated for its arteriogenic 
      efficacy, the adipocytokine leptin. METHODS AND RESULTS: Forty-two New Zealand 
      White rabbits received either MCP-1, leptin or PBS after ligation of the right 
      femoral artery. The pro-arteriogenic effect of MCP-1 was confirmed by flow 
      measurements during reactive hyperemia, as demonstrated by increased flow ratio 
      (PBS 0.56+/-0.07 vs. MCP-1 0.77+/-0.06, no unit, p<0.0001), ankle-brachial index 
      and microsphere-based conductance measurements (PBS 50.8+/-2.1 vs. MCP-1 
      225.8+/-8.8 ml/min/100 mm Hg, p<0.001). Biological activity of leptin on rabbit 
      monocytes was shown by a dose dependent increase in Mac-1 expression. In-vivo 
      administration of leptin also led to an increase in hyperemic flow and flow ratio 
      (leptin 0.69+/-0.03, p<0.05 vs. PBS), but not to an increase in collateral 
      conductance (leptin 54.7+/-4.1 ml/min/100 mm Hg, p=ns vs. PBS) or proliferation 
      of vascular smooth muscle cells (Ki-67 staining: PBS 24.7+/-3.9%, leptin 
      22.7%+/-0.8% (p=ns), MCP-1 32.0+/-1.9% (p<0.01)). Ki-67 mRNA measured by 
      real-time polymerase chain reaction increased (8.8+/-3.1-fold, p<0.01) during 
      natural arteriogenesis, and was further enhanced (25.5+/-8.1-fold, p<0.005) after 
      stimulation with MCP-1. CONCLUSION: MCP-1 and leptin increase collateral flow in 
      the rabbit hind limb model. In contrast to MCP-1, leptin does not enhance direct 
      markers of vascular proliferation such as collateral conductance under maximal 
      vasodilation and proliferation indices. The observed increase in hyperemic 
      collateral flow thus most probably can be attributed to the well-documented 
      vasodilatory effects of leptin. These data stress the necessity of the use of 
      proliferation markers and microsphere-based conductance measurements under 
      maximal vasodilation in order to separate effects of substances on vascular 
      proliferation from effects on vasodilation.
FAU - Schirmer, Stephan H
AU  - Schirmer SH
AD  - Research Group for Experimental and Clinical Arteriogenesis, Department of 
      Internal Medicine III-Cardiology and Angiology, University Hospital Freiburg, 
      Breisacher Strasse 66 (ZKF), D-79106 Freiburg, Germany. 
      Schirmer@med1.uni-freiburg.de
FAU - Buschmann, Ivo R
AU  - Buschmann IR
FAU - Jost, Marco M
AU  - Jost MM
FAU - Hoefer, Imo E
AU  - Hoefer IE
FAU - Grundmann, Sebastian
AU  - Grundmann S
FAU - Andert, Jan-Philip
AU  - Andert JP
FAU - Ulusans, Susann
AU  - Ulusans S
FAU - Bode, Christoph
AU  - Bode C
FAU - Piek, Jan J
AU  - Piek JJ
FAU - van Royen, Niels
AU  - van Royen N
LA  - eng
PT  - Journal Article
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Leptin)
RN  - 0 (Recombinant Proteins)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Animals
MH  - Arteries
MH  - Cell Line
MH  - Chemokine CCL2/*pharmacology
MH  - Collateral Circulation/*drug effects
MH  - Endothelium, Vascular/*drug effects/metabolism
MH  - Hindlimb
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - Leptin/*pharmacology
MH  - Neovascularization, Physiologic/*drug effects
MH  - Nitric Oxide/analysis/metabolism
MH  - Polymerase Chain Reaction/methods
MH  - Rabbits
MH  - Recombinant Proteins/pharmacology
MH  - Regional Blood Flow/drug effects
EDAT- 2004/10/16 09:00
MHDA- 2005/01/11 09:00
CRDT- 2004/10/16 09:00
PHST- 2004/01/13 00:00 [received]
PHST- 2004/06/07 00:00 [revised]
PHST- 2004/06/24 00:00 [accepted]
PHST- 2004/10/16 09:00 [pubmed]
PHST- 2005/01/11 09:00 [medline]
PHST- 2004/10/16 09:00 [entrez]
AID - S0008-6363(04)00279-2 [pii]
AID - 10.1016/j.cardiores.2004.06.022 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2004 Nov 1;64(2):356-64. doi: 10.1016/j.cardiores.2004.06.022.