HSP20 phosphorylation and interstitial metabolites in hypoxia-induced dilation of swine coronary arteries.
HSP20 phosphorylation and interstitial metabolites in hypoxia-induced dilation of swine coronary arteries.
复制标题
缺氧诱导的猪冠状动脉扩张中的 HSP20 磷酸化和间质代谢物。
DOI：
10.1111/j.1365-201x.2005.01426.x
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Rembold,CM
中科院分区：
文献类型：
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作者：
Frøbert,O;Buus,CL;Rembold,CM
目的：缺氧诱导冠状动脉扩张，但其机制尚不清楚。许多刺激通过减少ser19 - myosin调节轻链（MLC）磷酸化诱导动脉平滑肌松弛。其他刺激可以诱导平滑肌松弛而不降低ser19‐MLC磷酸化。这种形式的松弛被称为力抑制，似乎与热休克蛋白20 (HSP20) ser16上的磷酸化有关。我们研究了缺氧诱导的猪冠状动脉持续扩张是否在没有ser19‐MLC去磷酸化和ser16‐HSP20磷酸化的情况下被促进。硝酸甘油血管舒张术作为对照组。方法：在压力肌图中，使用微透析导管插管完整的预收缩（PGF2α; 10−5m）猪冠状动脉段的中膜。在90分钟缺氧、缺氧+再氧合（60分钟）、硝酸甘油（100μm， 90分钟）和硝酸甘油+冲洗（60分钟）时，研究直径反应和间质乳酸/丙酮酸比值。将动脉段快速冷冻并分析ser16‐HSP20磷酸化和ser19‐MLC磷酸化。结果：缺氧时归一化管径（6.1±4.3%）和硝酸甘油时归一化管径（12.6±1.6%）均显著大于常氧对照动脉（- 10.5±1.8%，方差分析，P< 0.05）。Ser16‐HSP20磷酸化随着缺氧和硝酸甘油处理而增加，Ser16‐HSP20磷酸化与直径变化相关（n= 29,r2= 0.64，P< 0.001）。Ser19‐MLC磷酸化未因缺氧而显著改变。乳酸/丙酮酸比值在缺氧动脉中显著升高，但与动脉直径或ser16‐HSP20磷酸化无关。结论：Ser16‐HSP20磷酸化是缺氧诱导冠状动脉扩张的潜在调节因子。
Objective:Hypoxia induces coronary artery dilation, but the responsible mechanism is largely unknown. Many stimuli induce arterial smooth muscle relaxation by reducing ser19‐myosin regulatory light chain (MLC) phosphorylation. Other stimuli can induce smooth muscle relaxation without reductions in ser19‐MLC phosphorylation. This form of relaxation has been termed force suppression and appears to be associated with heat shock protein 20 (HSP20) phosphorylation on ser16. We investigated whether hypoxia‐induced sustained dilation in swine coronary arteries was promoted without ser19‐MLC dephosphorylation and associated with ser16‐HSP20 phosphorylation. Nitroglycerin vasodilation served as control.Methods:In a pressure myograph, the tunica media of intact pre‐contracted (PGF2α; 10−5m) porcine coronary artery segments were cannulated using a microdialysis catheter. Diameter responses and interstitial lactate/pyruvate ratios were studied during 90 min hypoxia, hypoxia + reoxygenation (60 min), nitroglycerin (100μm, 90 min), and nitroglycerin + wash‐out (60 min). The arterial segments were snap‐frozen and analysed for ser16‐HSP20 phosphorylation and ser19‐MLC phosphorylation.Results:The normalized diameter responses to hypoxia (6.1 ± 4.3%) and nitroglycerin (12.6 ± 1.6%) were both significantly greater than normoxic control arteries (−10.5 ± 1.8%,anova,P< 0.05). Ser16‐HSP20 phosphorylation was increased with hypoxia and nitroglycerin treatment and ser16‐HSP20 phosphorylation correlated with changes in diameters (n= 29,r2= 0.64,P< 0.001). Ser19‐MLC phosphorylation was not significantly altered by hypoxia. The lactate/pyruvate ratio was significantly increased in hypoxic arteries but did not correlate with diameters or ser16‐HSP20 phosphorylation.Conclusion:Ser16‐HSP20 phosphorylation is a potential regulator of hypoxia‐induced dilation in coronary arteries.