Overexpression of CD39/nucleoside Triphosphate Diphosphohydrolase-1 Decreases Smooth Muscle Cell Proliferation and Prevents Neointima Formation After Angioplasty

Overview

Journal J Thromb Haemost

Publisher Elsevier

Specialty Hematology

Date 2008 May 20

PMID 18485080

Citations 9

Authors

K Koziak

M Bojakowska

S C Robson

K Bojakowski

J Soin

E Csizmadia

P Religa

Z Gaciong

E Kaczmarek

Affiliations

Soon will be listed here.

Abstract

Background: Growing evidence implicates the involvement of extracellular nucleotides in the regulation of platelet, leukocyte, endothelial cell (EC) and vascular smooth muscle cell (VSMC) phenotype and function. Within the quiescent vasculature, extracellular nucleotides are rapidly hydrolyzed by CD39, the dominant endothelial nucleoside triphosphate diphosphohydrolase (NTPDase-1). However, vascular CD39/NTPDase-1 activity is lost in EC activated by oxidative stress or proinflammatory mediators, and upon denudation of the endothelium following balloon injury. The consequent increase in extracellular nucleotide concentrations triggers signaling events leading to prothrombotic responses and increased VSMC proliferation.

Objectives: To investigate the effect of overexpressed CD39/NTPDase-1 in injured aorta.

Methods: Using adenoviral-mediated gene transfer we expressed CD39/NTPDase-1 in mechanically denudated rat aortas. We measured intima formation by morphometry and VSMC proliferation by the [(3)H]-thymidine incorporation assay.

Results: Targeted expression of CD39 in injured vessels increased NTPDase activity (from 2.91 +/- 0.31 to 22.07 +/- 6.7 nmols Pi mg(-1) protein, 4 days after exposure to the adenovirus) and prevented the formation of neointima. The thickness of the intimal layer in injured aortas exposed to Ad-CD39 was 26.2 +/- 3.9 microm vs. 51.8 +/- 6.1 microm and 64.4 +/- 22.2 microm (P < 0.001) in vessels treated with Ad-beta-gal and saline, respectively. Moreover, targeted expression of CD39/NTPDase-1 caused a 70% (P < 0.01) decrease in proliferation of VSMC isolated from transduced rat aortas as compared with VSMC derived from control vessels.

Conclusions: The presented data suggest that increasing CD39/NTPDase-1 activity in VSMC could represent a novel therapeutic approach for the prevention of stenosis associated with angioplasty and other occlusive vascular diseases.

Citing Articles

Inhibition of Vascular Smooth Muscle Cell Proliferation by ENPP1: The Role of CD73 and the Adenosine Signaling Axis.

Tchernychev B, Nitschke Y, Chu D, Sullivan C, Flaman L, OBrien K Cells. 2024; 13(13.

PMID: 38994980 PMC: 11240470. DOI: 10.3390/cells13131128.

NTPDase1/CD39 Ectonucleotidase Is Necessary for Normal Arterial Diameter Adaptation to Flow.

Favre J, Roy C, Guihot A, Drouin A, Laprise M, Gillis M Int J Mol Sci. 2023; 24(20).

PMID: 37894719 PMC: 10606763. DOI: 10.3390/ijms242015038.

NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female.

Babou Kammoe R, Kauffenstein G, Pelletier J, Robaye B, Sevigny J Biomolecules. 2021; 11(2).

PMID: 33498759 PMC: 7911947. DOI: 10.3390/biom11020147.

Ectonucleoside Triphosphate Diphosphohydrolase-1/CD39 Affects the Response to ADP of Female Rat Platelets.

Caiazzo E, Bilancia R, Rossi A, Ialenti A, Cicala C Front Pharmacol. 2020; 10:1689.

PMID: 32082171 PMC: 7005199. DOI: 10.3389/fphar.2019.01689.

ENPP1-Fc prevents neointima formation in generalized arterial calcification of infancy through the generation of AMP.

Nitschke Y, Yan Y, Buers I, Kintziger K, Askew K, Rutsch F Exp Mol Med. 2018; 50(10):1-12.

PMID: 30369595 PMC: 6204430. DOI: 10.1038/s12276-018-0163-5.

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