PMID- 20377367
OWN - NLM
STAT- MEDLINE
DCOM- 20100930
LR  - 20221207
IS  - 1557-7422 (Electronic)
IS  - 1043-0342 (Linking)
VI  - 20
IP  - 2
DP  - 2009 Feb
TI  - Recombinant adeno-associated virus-based gene transfer of cathelicidin induces 
      therapeutic neovascularization preferentially via potent collateral growth.
PG  - 159-67
LID - 10.1089/hum.2007.178 [doi]
AB  - Therapeutic neovascularization is a concept well validated in animal models, 
      however, without clear-cut success in clinical studies. To achieve prolonged 
      transgene expression, recombinant adeno-associated virus (rAAV) was used in a 
      chronic ischemic hind-limb model and the human antimicrobial peptide cathelicidin 
      (LL-37/hCAP-18) was used as proangiogenic factor. Seven days after femoral artery 
      excision, 0.5 x 10(11) rAAV particles encoding for green fluorescent protein 
      (rAAV.GFP), cathelicidin (rAAV.cath), or vascular endothelial growth factor A 
      (rAAV.VEGF-A) were retroinfused into the anterior tibial vein of rabbits (n = 5 
      per group). In addition, one rAAV.cath-treated group obtained a constant infusion 
      with the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin into the 
      ischemic tissue starting on day 7. On day 7 and day 35 angiography of both hind 
      limbs was performed for collateral quantification and frame count score 
      (cinedensitometry). Capillary-to-muscle fiber ratios were obtained on day 35. 
      Compared with controls, application of rAAV.cath induced a gain of perfusion (153 
      +/- 12 vs. 107 + 9% of day 7 controls) via increased collateral growth (length 
      index, 161 +/- 14 vs. 97 +/- 9%, controls), but no significant capillary growth 
      (1.16 +/- 0.09 vs. 0.99 +/- 0.08, controls). Wortmannin application completely 
      abolished the effects of rAAV.cath, indicating the involvement of the PI3K signal 
      pathway. In conclusion, rAAV-mediated cathelicidin expression is capable of 
      inducing functionally relevant neovascularization, preferentially by collateral 
      growth. The rAAV-based vectors as long-expressing vector expression systems and 
      cathelicidin as proangiogenic factor provide a promising new combination in the 
      treatment of peripheral artery disease.
FAU - Pinkenburg, Olaf
AU  - Pinkenburg O
AD  - Division of Pulmonology, Department of Internal Medicine, Hospital of the 
      University of Marburg, Philipps Universitat Marburg, Marburg, Germany.
FAU - Pfosser, Achim
AU  - Pfosser A
FAU - Hinkel, Rabea
AU  - Hinkel R
FAU - Bottcher, Martina
AU  - Bottcher M
FAU - Dinges, Claudia
AU  - Dinges C
FAU - Lebherz, Corinna
AU  - Lebherz C
FAU - Sultana, Shahana
AU  - Sultana S
FAU - Enssle, Jorg
AU  - Enssle J
FAU - El-Aouni, Chiraz
AU  - El-Aouni C
FAU - Buning, Hildegard
AU  - Buning H
FAU - Boekstegers, Peter
AU  - Boekstegers P
FAU - Bals, Robert
AU  - Bals R
FAU - Kupatt, Christian
AU  - Kupatt C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (Cathelicidins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Animals
MH  - Antimicrobial Cationic Peptides
MH  - Cathelicidins/*genetics/metabolism
MH  - Cells, Cultured
MH  - Dependovirus/*genetics
MH  - Disease Models, Animal
MH  - Gene Transfer Techniques
MH  - Hindlimb/blood supply
MH  - Humans
MH  - Ischemia/*therapy
MH  - Neovascularization, Physiologic/*genetics
MH  - Rabbits
MH  - Recombinant Proteins/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
EDAT- 2009/02/01 00:00
MHDA- 2010/10/01 06:00
CRDT- 2010/04/10 06:00
PHST- 2010/04/10 06:00 [entrez]
PHST- 2009/02/01 00:00 [pubmed]
PHST- 2010/10/01 06:00 [medline]
AID - 10.1089/hum.2007.178 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2009 Feb;20(2):159-67. doi: 10.1089/hum.2007.178.