Key result
Enhanced pulsatile pressure, including high pulse pressure and high pulse rate, significantly accelerated rat aortic vascular smooth muscle cell migration in vitro by 1.27 to 2.38-fold.
Why the study?
Does enhanced pulsatile pressure accelerate vascular smooth muscle cell migration in vitro?
Does enhanced pulsatile pressure accelerate vascular smooth muscle cell migration in vitro?
Enhanced pulsatile pressure directly accelerates vascular smooth muscle cell migration via calcium-dependent pathways, providing a mechanistic link between hypertension and atherogenesis.
Hypothesis-generating for pulsatile pressure in atherogenesis; requires in vivo and human validation before clinical relevance.
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 AND RESULTS: 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.
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Tada et al. (2008) studied Atherosclerosis / Hypertension. Enhanced pulsatile pressure vs. Static or lower pressures and pulse rates was evaluated on Vascular smooth muscle cell (VSMC) migration (1.27 to 2.38-fold increase). Enhanced pulsatile pressure, including high pulse pressure and high pulse rate, significantly accelerated rat aortic vascular smooth muscle cell migration in vitro by 1.27 to 2.38-fold.
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