Hoefer I E, van Royen N, Buschmann I R, Piek J J, Schaper W
Department of Experimental Cardiology, Max-Planck-Institute for Physiological and Clinical Research, Benekestr. 2, D-61231, Bad Nauheim, Germany.
Cardiovasc Res. 2001 Feb 16;49(3):609-17. doi: 10.1016/s0008-6363(00)00243-1.
We examined the time course of arteriogenesis (collateral artery growth) after femoral artery ligation and the effect of monocyte chemoattractant protein-1 (MCP-1).
New Zealand White rabbits received MCP-1 or phosphate buffered saline (PBS) for a 1-week period, either directly or 3 weeks after femoral artery ligation (non-ischemic model). A control group was studied with intact femoral arteries and another 1 min after acute femoral artery ligation.
Collateral conductance index significantly increased when MCP-1 treatment started directly after femoral artery ligation (acute occlusion: 0.94+/-0.19; without occlusion: 168.56+/-15.99; PBS: 4.10+/-0.48; MCP-1: 33.96+/-1.76 ml/min/100 mmHg). However, delayed onset of treatment 3 weeks after ligation and final study of conductance at 4 weeks showed no significant difference against a 4-week control (PBS: 79.08+/-7.24; MCP-1: 90.03+/-8.73 ml/min/100 mmHg). In these groups increased conductance indices were accompanied by a decrease in the number of visible collateral vessels (from 18 to 36 identifiable vessels at day 7 to about four at 21 days).
We conclude that the chemokine MCP-1 markedly accelerated collateral artery growth but did not alter its final extent above that reached spontaneously as a function of time. We show thus for the first time that a narrow time window exists for the responsiveness to the arteriogenic actions of MCP-1, a feature that MCP-1 may share with other growth factors. We show furthermore that the spontaneous adaptation by arteriogenesis stops when only about 50% of the vasodilatory reserve of the arterial bed before occlusion are reached. The superiority of few large arterial collaterals in their ability to conduct large amounts of blood flow per unit of pressure as compared to the angiogenic response where large numbers of small vessels are produced with minimal ability to allow mass transport of bulk flow is stressed.
我们研究了股动脉结扎后动脉生成（侧支动脉生长）的时间进程以及单核细胞趋化蛋白-1（MCP-1）的作用。
新西兰白兔在股动脉结扎后1周（非缺血模型）直接或3周接受MCP-1或磷酸盐缓冲盐水（PBS），为期1周。对完整股动脉的一组进行研究，并在急性股动脉结扎后1分钟对另一组进行研究。
当在股动脉结扎后直接开始MCP-1治疗时，侧支传导指数显著增加（急性闭塞：0.94±0.19；无闭塞：168.56±15.99；PBS：4.10±0.48；MCP-1：33.96±1.76 ml/min/100 mmHg）。然而，结扎3周后延迟开始治疗并在4周时最终研究传导，与4周对照组相比无显著差异（PBS：79.08±7.24；MCP-1：90.03±8.73 ml/min/100 mmHg）。在这些组中，传导指数增加伴随着可见侧支血管数量的减少（从第7天的18至36条可识别血管减少到21天时约4条）。
我们得出结论，趋化因子MCP-1显著加速了侧支动脉生长，但并未改变其最终程度，其最终程度不会超过随时间自发达到的程度。因此，我们首次表明，对MCP-1的动脉生成作用存在一个狭窄的时间窗，这一特征MCP-1可能与其他生长因子相同。我们还表明，当仅达到闭塞前动脉床血管舒张储备的约50%时，动脉生成的自发适应就会停止。强调了少数大的动脉侧支在单位压力下传导大量血流的能力优于生成大量小血管但允许大量血流进行质量传输能力最小的血管生成反应。
