Carbon dioxide-rich water bathing enhances collateral blood flow in ischemic hindlimb via mobilization of endothelial progenitor cells and activation of NO-cGMP system
Carbon dioxide-rich water bathing enhances collateral blood flow in ischemic hindlimb via mobilization of endothelial progenitor cells and activation of NO-cGMP system
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DOI：
10.1161/01.cir.0000159329.40098.66
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发表时间：
2005-03-29
期刊：
影响因子：
37.8
通讯作者：
Matsubara, H
中科院分区：
文献类型：
--
作者：
Irie, H;Tatsumi, T;Matsubara, H
背景-富含二氧化碳的水浴具有血管舒张作用，但该疗法是否发挥与新血管形成相关的血管生成作用仍不确定。方法和结果-通过切除C57BL/J小鼠的股动脉诱导单侧后肢缺血。将下肢浸入37℃的富CO2水（CO2浓度1000～1200mg/L）或淡水（对照）中10分钟，每天一次。激光多普勒成像显示，CO2 沐浴后缺血肢体的血液灌注增加（第 28 天增加 38%，P < 0.001），而 N-G-硝基-L-精氨酸甲酯治疗消除了这种效果。血管造影或免疫组织化学显示侧支血管形成和毛细血管密度增加（分别为4.1倍和3.7倍，P < 0.001）。第14天血浆血管内皮生长因子（VEGF）水平升高（18%，P<0.05）。沐浴 CO2 的后肢肌肉中 VEGF mRNA 水平、NO 合酶磷酸化和 cGMP 积累增加（分别为 2.7 倍、2.4 倍和 3.4 倍），但前肢肌肉中没有增加。 CO2 浴显着增加了循环 Lin-/Flk-1+/CD34- 内皮谱系祖细胞的数量（第 14 天时增加了 24 倍，P < 0.001）。 Lin-/Flk-1+/CD34- 细胞表达其他内皮抗原（内皮糖蛋白和 VE-钙粘蛋白）并掺入乙酰化 LDL。结论 - 我们目前的研究表明，缺血后肢的 CO2 浴会诱导局部 VEGF 合成，从而导致与内皮祖细胞动员相关的 NO 依赖性新毛细血管形成。
Background - Carbon dioxide - rich water bathing has the effect of vasodilatation, whereas it remains undetermined whether this therapy exerts an angiogenic action associated with new vessel formation.Methods and Results - Unilateral hindlimb ischemia was induced by resecting the femoral arteries of C57BL/J mice. Lower limbs were immersed in CO2-enriched water (CO2 concentration, 1000 to 1200 mg/L) or freshwater ( control) at 37 degrees C for 10 minutes once a day. Laser Doppler imaging revealed increased blood perfusion in ischemic limbs of CO2 bathing (38% increase at day 28, P < 0.001), whereas N-G-nitro-L-arginine methyl ester treatment abolished this effect. Angiography or immunohistochemistry revealed that collateral vessel formation and capillary densities were increased (4.1-fold and 3.7-fold, P < 0.001, respectively). Plasma vascular endothelial growth factor ( VEGF) levels were elevated at day 14 ( 18%, P < 0.05). VEGF mRNA levels, phosphorylation of NO synthase, and cGMP accumulation in the CO2-bathed hindlimb muscles were increased (2.7-fold, 2.4-fold, and 3.4-fold, respectively) but not in forelimb muscles. The number of circulating Lin-/Flk-1+/CD34- endothelial-lineage progenitor cells was markedly increased by CO2 bathing (24-fold at day 14, P < 0.001). The Lin-/Flk-1+/CD34- cells express other endothelial antigens ( endoglin and VE-cadherin) and incorporated acetylated LDL.Conclusions - Our present study demonstrates that CO2 bathing of ischemic hindlimb causes the induction of local VEGF synthesis, resulting in an NO-dependent neocapillary formation associated with mobilization of endothelial progenitor cells.