RESUMO
Rapid re-endothelialization following balloon angioplasty can reduce restenosis by inhibiting smooth muscle cell migration and proliferation. However, formation of a neointima following angioplasty can be inhibited due to endothelial cell dysfunction and denudation. The purpose of this study was to evaluate mechanical tensile stress as a cause of endothelial cell dysfunction. The Flexercell strain unit was utilized to generate both short-term cyclic and static tensile strain on cultured bovine aortic endothelial cells (BAECs). Before analysis of this loading on BAECs, strain behaviour of the Flexercell system and DNA assay conditions were optimized. This paper demonstrates that, when compared with unloaded controls, 4-h cyclic loading at 4 per cent elongation and 0.1 Hz, and static loading at 4 per cent elongation cause a 44 and 70 per cent decrease in DNA synthesis respectively. In a companion paper, it is demonstrated that low DNA synthesis levels in mechanically loaded cells can be increased by incubation with Ap4A and/or NO donors.
Assuntos
DNA/biossíntese , Endotélio Vascular/fisiologia , Mecanotransdução Celular/fisiologia , Suporte de Carga/fisiologia , Animais , Aorta/citologia , Aorta/fisiologia , Bovinos , Contagem de Células/métodos , Tamanho Celular/fisiologia , Sobrevivência Celular/fisiologia , Células Cultivadas , DNA/análise , Elasticidade , Endotélio Vascular/citologia , Pressão , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estresse Mecânico , Resistência à TraçãoRESUMO
Rapid re-endothelialization following balloon angioplasty can reduce restenosis by inhibiting smooth muscle cell migration and proliferation. However, formation of a neointima layer following angioplasty can be inhibited due to endothelial cell dysfunction and denudation. In a companion paper, it has been illustrated that mechanical loading causes a decrease in DNA synthesis in bovine aortic endothelial cells (BAECs) thus rendering them dysfunctional. The purpose of this study was to overcome BAEC dysfunction by incubation with pharmacological agents to increase DNA synthesis. Previous studies demonstrated that the adenosine dinucleotides Ap4A and Ap2A induced nitric oxide (NO) production from BAEC while Ap3A, Ap5A and Ap6A did not. This paper demonstrates that Ap4A and Ap2A induce a 1.46- and 1.16-fold increase in DNA synthesis in mechanically stressed BAECs respectively, while Ap3A, Ap5A and Ap6A do not. Additionally, NOC-18, a slow NO release NO donor, significantly increases DNA synthesis in mechanically stressed BAECs without affecting unloaded cells. These results are consistent with NO inducing DNA synthesis in mechanically stressed BAECs.
