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Intimal Hyperplasia in Balloon Dilated Coronary Arteries is Reduced by Local Delivery of the NO Donor, SIN-1 Via a cGMP-Dependent Pathway.

Harnek, Jan LU ; Zoucas, Evita; Perez de Sá, Valéria LU ; Ekblad, Eva LU ; Arner, Anders LU and Stenram, Unne LU (2011) In BMC Cardiovascular Disorders 11(1).
Abstract
BACKGROUND:



To elucidate the mechanism by which local delivery of 3-morpholino-sydnonimine (SIN-1) affects intimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA).

METHODS:



Porcine coronary arteries were treated with PTCA and immediately afterwards locally treated for 5 minutes, with a selective cytosolic guanylate cyclase inhibitor, 1 H-(1,2,4)oxadiazole(4,3-alpha)quinoxaline-1-one (ODQ) + SIN-1 or only SIN-1 using a drug delivery-balloon. Arteries were angiographically depicted, morphologically evaluated and analyzed after one and eight weeks for actin, myosin and intermediate filaments (IF) and nitric oxide synthase (NOS) contents.

RESULTS:

... (More)
BACKGROUND:



To elucidate the mechanism by which local delivery of 3-morpholino-sydnonimine (SIN-1) affects intimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA).

METHODS:



Porcine coronary arteries were treated with PTCA and immediately afterwards locally treated for 5 minutes, with a selective cytosolic guanylate cyclase inhibitor, 1 H-(1,2,4)oxadiazole(4,3-alpha)quinoxaline-1-one (ODQ) + SIN-1 or only SIN-1 using a drug delivery-balloon. Arteries were angiographically depicted, morphologically evaluated and analyzed after one and eight weeks for actin, myosin and intermediate filaments (IF) and nitric oxide synthase (NOS) contents.

RESULTS:



Luminal diameter after PCI in arteries treated with SIN-1 alone and corrected for age-growth was significantly larger as compared to ODQ + SIN-1 or to controls (p < 0.01). IF/actin ratio after one week in SIN-1 treated segments was not different compared to untreated segments, but was significantly reduced compared to ODQ + SIN-1 treated vessels (p < 0.05). Expression of endothelial NADPH diaphorase activity was significantly lower in untreated segments and in SIN-1 treated segments compared to controls and SIN-1 + ODQ treated arteries (p < 0.01). Restenosis index (p < 0.01) and intimal hyperplasia (p < 0.01) were significantly reduced while the residual lumen was increased (p < 0.01) in SIN-1 segments compared to controls and ODQ + SIN-1 treated vessels.

CONCLUSIONS:



After PTCA local delivery of high concentrations of the NO donor SIN-1 for 5 minutes inhibited injury induced neointimal hyperplasia. This favorable effect was abolished by inhibition of guanylyl cyclase indicating mediation of a cyclic guanosine 3',5'-monophosphate (cGMP)-dependent pathway. The momentary events at the time of injury play crucial role in the ensuring development of intimal hyperplasia. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BMC Cardiovascular Disorders
volume
11
issue
1
publisher
BioMed Central
external identifiers
  • WOS:000292036700001
  • PMID:21663688
  • Scopus:79958087169
ISSN
1471-2261
DOI
10.1186/1471-2261-11-30
language
English
LU publication?
yes
id
4f9196d5-826c-4cb5-b0d2-1cbfc200d76b (old id 2008202)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21663688?dopt=Abstract
date added to LUP
2011-07-04 13:46:37
date last changed
2016-10-13 04:23:19
@misc{4f9196d5-826c-4cb5-b0d2-1cbfc200d76b,
  abstract     = {BACKGROUND:<br/><br>
<br/><br>
To elucidate the mechanism by which local delivery of 3-morpholino-sydnonimine (SIN-1) affects intimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA).<br/><br>
METHODS:<br/><br>
<br/><br>
Porcine coronary arteries were treated with PTCA and immediately afterwards locally treated for 5 minutes, with a selective cytosolic guanylate cyclase inhibitor, 1 H-(1,2,4)oxadiazole(4,3-alpha)quinoxaline-1-one (ODQ) + SIN-1 or only SIN-1 using a drug delivery-balloon. Arteries were angiographically depicted, morphologically evaluated and analyzed after one and eight weeks for actin, myosin and intermediate filaments (IF) and nitric oxide synthase (NOS) contents.<br/><br>
RESULTS:<br/><br>
<br/><br>
Luminal diameter after PCI in arteries treated with SIN-1 alone and corrected for age-growth was significantly larger as compared to ODQ + SIN-1 or to controls (p &lt; 0.01). IF/actin ratio after one week in SIN-1 treated segments was not different compared to untreated segments, but was significantly reduced compared to ODQ + SIN-1 treated vessels (p &lt; 0.05). Expression of endothelial NADPH diaphorase activity was significantly lower in untreated segments and in SIN-1 treated segments compared to controls and SIN-1 + ODQ treated arteries (p &lt; 0.01). Restenosis index (p &lt; 0.01) and intimal hyperplasia (p &lt; 0.01) were significantly reduced while the residual lumen was increased (p &lt; 0.01) in SIN-1 segments compared to controls and ODQ + SIN-1 treated vessels.<br/><br>
CONCLUSIONS:<br/><br>
<br/><br>
After PTCA local delivery of high concentrations of the NO donor SIN-1 for 5 minutes inhibited injury induced neointimal hyperplasia. This favorable effect was abolished by inhibition of guanylyl cyclase indicating mediation of a cyclic guanosine 3',5'-monophosphate (cGMP)-dependent pathway. The momentary events at the time of injury play crucial role in the ensuring development of intimal hyperplasia.},
  author       = {Harnek, Jan and Zoucas, Evita and Perez de Sá, Valéria and Ekblad, Eva and Arner, Anders and Stenram, Unne},
  issn         = {1471-2261},
  language     = {eng},
  number       = {1},
  publisher    = {ARRAY(0x9014408)},
  series       = {BMC Cardiovascular Disorders},
  title        = {Intimal Hyperplasia in Balloon Dilated Coronary Arteries is Reduced by Local Delivery of the NO Donor, SIN-1 Via a cGMP-Dependent Pathway.},
  url          = {http://dx.doi.org/10.1186/1471-2261-11-30},
  volume       = {11},
  year         = {2011},
}