Myosin phosphatase isoforms and related transcripts in the pig coronary circulation and effects of exercise and chronic occlusion.
Myosin phosphatase isoforms and related transcripts in the pig coronary circulation and effects of exercise and chronic occlusion.
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DOI：
10.1016/j.mvr.2014.02.004
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发表时间：
2015-03
影响因子：
3.1
通讯作者：
Fisher, Steven A.
中科院分区：
文献类型：
--
作者：
Zheng, Xiaoxu;Heaps, Cristine L.;Fisher, Steven A.
肌球蛋白磷酸酶（MP）是调节平滑肌张力和血流的信号通路的关键靶标。MP靶向亚基（MYPT 1）外显子24（E24）的选择性剪接产生具有NO/cGMP激活MP所需的C-末端亮氨酸拉链（LZ）的可变存在的亚型。在这里，我们研究了冠状动脉循环疾病模型中MP和相关基因的表达。雌性尤卡坦小型猪在左回旋支（LCX）动脉周围放置Ameroid缩窄器后8周开始保持久坐或进行运动训练。14周后，采集心外膜动脉（~1 mm）和阻力小动脉（~125 µm）并测定基因表达。MYPT 1亚型在心外膜动脉（E24−/LZ+）和阻力小动脉（E24+/LZ−）中是不同的，并且不受运动训练或冠状动脉闭塞的影响。MYPT 1、CPI-17和PDE 5 mRNA水平在动脉和小动脉之间没有差异，而Kir2.1和eNOS在小动脉中分别高6.6倍和3.9倍。在心外膜动脉的侧支（LCX）与非闭塞的左前降支（LAD）区域，或在运动训练的猪与久坐的猪中，转录本丰度没有显著变化。有一个显着的CPI-17增加1.2倍，在侧支依赖性小动脉，独立于运动，和一个显着的1.7倍增加PDE 5在小动脉从运动训练的猪，独立于闭塞。我们得出结论，MYPT 1 E24（LZ）亚型，eNOS和Kir2.1的差异区分心外膜动脉和阻力冠状动脉。运动引起的冠状小动脉PDE 5和慢性闭塞引起的CPI-17的上调可能有助于改变血管反应，需要进一步研究。
Myosin phosphatase (MP) is a key target of signaling pathways that regulate smooth muscle tone and blood flow. Alternative splicing of MP targeting subunit (MYPT1) exon 24 (E24) generates isoforms with variable presence of a C-terminal leucine zipper (LZ) required for activation of MP by NO/cGMP. Here we examined the expression of MP and associated genes in a disease model in the coronary circulation. Female Yucatan miniature swine remained sedentary or were exercise-trained beginning eight weeks after placement of an ameroid constrictor around the left circumflex (LCX) artery. Fourteen weeks later epicardial arteries (~1 mm) and resistance arterioles (~125 µm) were harvested and assayed for gene expression. MYPT1 isoforms were distinct in the epicardial arteries (E24−/LZ+) and resistance arterioles (E24+/LZ−) and unchanged by exercise training or coronary occlusion. MYPT1, CPI-17 and PDE5 mRNA levels were not different between arteries and arterioles while Kir2.1 and eNOS were 6.6-fold and 3.9-fold higher in the arterioles. There were no significant changes in transcript abundance in epicardial arteries of the collateralized (LCX) vs. non-occluded left anterior descending (LAD) territories, or in exercise-trained vs. sedentary pigs. There was a significant 1.2 fold increase in CPI-17 in collateral-dependent arterioles, independent of exercise, and a significant 1.7 fold increase in PDE5 in arterioles from exercise-trained pigs, independent of occlusion. We conclude that differences in MYPT1 E24 (LZ) isoforms, eNOS, and Kir2.1 distinguish epicardial arteries and resistance coronary arterioles. Up-regulation of coronary arteriolar PDE5 by exercise and CPI-17 by chronic occlusion could contribute to altered vasomotor responses and requires further study.
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DOI：
10.1152/ajpheart.00792.2002
发表时间：
2003-04-01
影响因子：
4.8
作者：
Laughlin, MH;Turk, JR;Price, EM
通讯作者：
Price, EM
影响因子：
5.5
作者：
Lu, Yuan;Zhang, Haiying;Fisher, Steven A.
通讯作者：
Fisher, Steven A.
影响因子：
3.3
作者：
de Beer, Vincent J.;Merkus, Daphne;Laughlin, M. Harold
通讯作者：
Laughlin, M. Harold
影响因子：
3.5
作者：
Bhetwal BP;An CL;Fisher SA;Perrino BA
通讯作者：
Perrino BA
DOI：
10.1152/ajpheart.2000.278.6.h1984
发表时间：
2000-06-01
影响因子：
4.8
作者：
Heaps, CL;Sturek, M;Parker, JL
通讯作者：
Parker, JL