Extracellular adenosine induces apoptosis of human arterial smooth muscle cells via A(2b)-purinoceptor

Citation
Ml. Peyot et al., Extracellular adenosine induces apoptosis of human arterial smooth muscle cells via A(2b)-purinoceptor, CIRCUL RES, 86(1), 2000, pp. 76-85
Citations number
64
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
CIRCULATION RESEARCH
ISSN journal
00097330 → ACNP
Volume
86
Issue
1
Year of publication
2000
Pages
76 - 85
Database
ISI
SICI code
0009-7330(20000107)86:1<76:EAIAOH>2.0.ZU;2-K
Abstract
Apoptosis of arterial smooth muscle cells (ASMCs) could play an important r ole in the pathogenesis of atherosclerosis and restenosis. Recent studies h ave demonstrated that extracellular adenosine induces apoptosis in various cell types. Our aim was to delineate the capacity of this nucleoside to ind uce ASMC apoptosis in arterial diseases. We demonstrate that adenosine dose -dependently triggers apoptosis of cultured human ASMCs. Apoptotic cell dea th was quantified by analysis of nuclear chromatin morphology and character ized by DNA laddering. The involvement of adenosine receptors was suggested , because neither an adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3- nonyl) adenine hydrochloride, nor an inhibitor of cellular nucleoside trans port, dipyridamole, was able to inhibit adenosine-induced ASMC apoptosis. I n contrast, an A(1)/A(2)-adenosine receptor antagonist, xanthine amine cong ener, totally inhibited adenosine-induced apoptosis. Furthermore, among mor e selective inhibitors of P-1, purinoceptor subtypes, only alloxazine, an a ntagonist of A(1)- and A(2)-adenosine receptors, completely inhibited adeno sine-induced ASMC apoptosis, suggesting that adenosine triggers ASMC apopto sis via either 1 or both of these receptors. However, 8-cyclopentyl-1,3-dip ropylxanthine, 8-(3-chlorostyryl) caffeine, and 3-ethyl-5-benzyl-2-methyl-4 phenylethynyl-6-phenyl- 1,4-(+/-)-dihydropyridine-3,5-dicarboxylate, which are A(1)-, A(2n)-, and A(3)-adenosine receptor antagonists, did not inhibit adenosine-induced apoptosis, suggesting an involvement of the A(2b)-recept or in this process. Moreover, the cAMP increase followed by cAMP-dependent protein kinase activation appears essential to mediate adenosine-induced AS MC apoptosis, thus confirming the previous hypothesis. These results indica te that adenosine-induced apoptosis of ASMCs is essentially mediated via A( 2b)-adenosine receptor and involves a cAMP-dependent pathway.