Enhanced pulsatile pressure accelerates vascular smooth muscle migration: implications for atherogenesis of hypertension.
Cardiovasc Res
; 80(3): 346-53, 2008 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-18687705
ABSTRACT
AIMS:
Clinical studies have suggested that pulsatile pressure is an independent risk factor for atherosclerosis. However, it is unknown whether enhanced pulsatile pressure per se directly accelerates vascular smooth muscle cell (VSMC) migration, an important process of atherosclerosis. METHODS ANDRESULTS:
Using our original Pressure-loading system with a Boyden chamber, we examined the direct effects of variable pressures and pulse rates on migration of rat aortic VSMCs in vitro. High pulse pressure (180/90 mmHg, pulsatile vs. 180 mmHg, static), high mean pressure (180/90 vs. 90/0 mmHg, with the same pulse pressure), wide pulse pressure (190/110 vs. 170/130 mmHg, with the same mean pressure), and high pulse rate (120 vs. 40 per min) significantly accelerated the VSMC migration (1.35, 2.38, 1.38 and 1.27-fold, respectively). The increase in intracellular calcium levels measured by fura-2/AM fluorescence was proportional to the magnitude of pressure loaded. The pressure-promoted VSMC migration was significantly inhibited by a phospholipase-C inhibitor U-73122 or a calmodulin inhibitor W-7. Inositol 1,4,5-trisphosphate receptor blockers 2-aminoethoxydiphenyl borate or xestospongin-C significantly inhibited the VSMC migration, whereas a ryanodine receptor blocker ryanodine had no effects. Furthermore, a calcium channel blocker (CCB), azelnidipine, and an angiotensin type-1 receptor blocker, olmesartan, also significantly inhibited the VSMC migration.CONCLUSION:
These results provide direct evidence for the pro-atherogenic effects of enhanced pulsatile pressure and also suggest that the anti-atherogenic actions of CCBs and angiotensin type-1 receptor blockers are mediated in part by their direct inhibitory effects on VSMC migration in addition to their anti-hypertensive effects.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Presión Sanguínea
/
Movimiento Celular
/
Aterosclerosis
/
Hipertensión
/
Músculo Liso Vascular
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Cardiovasc Res
Año:
2008
Tipo del documento:
Article
País de afiliación:
Japón