Widespread Coronary Dysfunction in the Absence of HDL Receptor SR-B1 in an Ischemic Cardiomyopathy Mouse Model.
Widespread Coronary Dysfunction in the Absence of HDL Receptor SR-B1 in an Ischemic Cardiomyopathy Mouse Model.
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DOI：
10.1038/s41598-017-18485-6
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发表时间：
2017-12-22
影响因子：
4.6
通讯作者：
Shirai M
中科院分区：
文献类型：
--
作者：
Pearson JT;Yoshimoto M;Chen YC;Sultani R;Edgley AJ;Nakaoka H;Nishida M;Umetani K;Waddingham MT;Jin HL;Zhang Y;Kelly DJ;Schwenke DO;Inagaki T;Tsuchimochi H;Komuro I;Yamashita S;Shirai M
高密度脂蛋白清道夫受体B1（SR-B1）对脂蛋白的清除减少在闭塞性冠状动脉疾病中起重要作用。然而，目前尚不清楚微血管功能障碍在多大程度上导致缺血性心肌病。我们的目的是确定在短暂暴露于Paigen高脂饮食后，雄性小鼠的冠状动脉循环中的血管功能障碍在体内的分布，以及这种血管功能障碍是否涉及一氧化氮（NO）和/或内皮源性超极化因子（EDHF）。我们使用了缺乏SR-B1（SR-B1−/−/ApoER 61 h/h，n = 8）或SR-B1杂合子（SR-B1+/−/ApoER 61 h/h，n = 8）的亚型ApoE脂蛋白小鼠，通过同步加速器微血管造影术研究冠状动脉扩张功能。仅在SR-B1缺陷小鼠体内观察到部分闭塞性狭窄。SR-B1缺陷小鼠动脉小动脉口径增加乙酰胆碱和硝普钠刺激不存在。在L-NAME（50 mg/kg）和甲氨蝶呤钠（3 mg/kg）阻断后，两组小鼠中均存在对乙酰胆碱的残余扩张，但闭塞处除外，表明EDHF未受损。我们发现，SR-B1缺乏造成损害的NO介导的扩张的电导和微血管。我们的研究结果还表明，EDHF和前列腺素类是重要的全球灌注，但最终的损失NO介导的血管舒张有助于动脉粥样硬化血栓进展缺血性心肌病。
Reduced clearance of lipoproteins by HDL scavenger receptor class B1 (SR-B1) plays an important role in occlusive coronary artery disease. However, it is not clear how much microvascular dysfunction contributes to ischemic cardiomyopathy. Our aim was to determine the distribution of vascular dysfunction in vivo in the coronary circulation of male mice after brief exposure to Paigen high fat diet, and whether this vasomotor dysfunction involved nitric oxide (NO) and or endothelium derived hyperpolarization factors (EDHF). We utilised mice with hypomorphic ApoE lipoprotein that lacked SR-B1 (SR-B1−/−/ApoER61h/h, n = 8) or were heterozygous for SR-B1 (SR-B1+/−/ApoER61h/h, n = 8) to investigate coronary dilator function with synchrotron microangiography. Partially occlusive stenoses were observed in vivo in SR-B1 deficient mice only. Increases in artery-arteriole calibre to acetylcholine and sodium nitroprusside stimulation were absent in SR-B1 deficient mice. Residual dilation to acetylcholine following L-NAME (50 mg/kg) and sodium meclofenamate (3 mg/kg) blockade was present in both mouse groups, except at occlusions, indicating that EDHF was not impaired. We show that SR-B1 deficiency caused impairment of NO-mediated dilation of conductance and microvessels. Our findings also suggest EDHF and prostanoids are important for global perfusion, but ultimately the loss of NO-mediated vasodilation contributes to atherothrombotic progression in ischemic cardiomyopathy.
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DOI：
10.1161/atvbaha.114.304200
发表时间：
2014-11-01
影响因子：
8.7
作者：
Fuller, Mark;Dadoo, Omid;Trigatti, Bernardo L.
通讯作者：
Trigatti, Bernardo L.
DOI：
10.1152/ajpheart.00179.2014
发表时间：
2014-06-15
影响因子：
4.8
作者：
Feher, Attila;Broskova, Zuzana;Bagi, Zsolt
通讯作者：
Bagi, Zsolt
影响因子：
20.1
作者：
Behringer EJ;Segal SS
通讯作者：
Segal SS
影响因子：
5.3
作者：
Hein, Travis W.;Singh, Uma;Vasquez-Vivar, Jeannette;Devaraj, Sridevi;Kuo, Lih;Jialal, Ishwarlal
通讯作者：
Jialal, Ishwarlal
影响因子：
4.8
作者：
Li, XM;Li, RH;Guan, MX
通讯作者：
Guan, MX