Yang Bo, Fan Pengcheng, Xu Aimin, Lam Karen Sl, Berger Thorsten, Mak Tak W, Tse Hung-Fat, Yue Jessie Ws, Song Erfei, Vanhoutte Paul M, Sweeney Gary, Wang Yu
Am J Transl Res. 2012;4(1):60-71. Epub 2012 Jan 5.
Recent clinical and experimental evidences demonstrate an association between augmented circulating lipocalin-2 [a pro-inflammatory adipokine] and cardiac dysfunction. However, little is known about the pathophysi-ological role of lipocalin-2 in heart. The present study was designed to compare the heart functions of mice with normal (WT) or deficient lipocalin-2 (Lcn2-KO) expression.
Echocardiographic analysis revealed that the myocardial contractile function was significantly improved in hearts of Lcn2-KO mice, under both standard chow and high fat diet conditions. The heart function before and after I/R injury (20-min of global ischemia followed by 60-min of reperfusion) was assessed using the Langendorff perfusion system. Compared to WT littermates, hearts from Lcn2-KO mice showed improved functional recovery and reduced infarct size following I/R. Under baseline condition, the mitochondrial function of Lcn2-KO hearts was significantly enhanced, as demonstrated by biochemical analysis of respiratory chain activity and markers of biogenesis, as well as electron microscopic investigation of the mitochondrial ultrastructure. Acute or chronic administration of lipocalin-2 impaired cardiac functional recovery to I/R and dampened the mitochondrial function in hearts of Lcn2-KO mice. These effects were associated with an extensive modification of the fatty acyl chain compositions of intracellular phospholipids. For example, lipocalin-2 facilitated the redistribution of linoleic acid (C18:2) among different types of phospholipids, including cardiolipin, a structurally unique phospholipid located mainly on the inner membrane of mitochondria.
Lack of lipocalin-2 improved the functional recovery of isolated mice hearts subjected to I/R, which is associated with restoration of mitochondrial function and phospholipids remodeling.
近期临床和实验证据表明，循环中脂联素-2（一种促炎脂肪因子）水平升高与心脏功能障碍之间存在关联。然而，关于脂联素-2在心脏中的病理生理作用知之甚少。本研究旨在比较脂联素-2表达正常（野生型，WT）或缺乏（Lcn2基因敲除，Lcn2-KO）的小鼠的心脏功能。
超声心动图分析显示，在标准饲料和高脂饮食条件下，Lcn2-KO小鼠心脏的心肌收缩功能均显著改善。使用Langendorff灌注系统评估缺血/再灌注损伤（20分钟全心缺血后再灌注60分钟）前后的心脏功能。与野生型同窝小鼠相比，Lcn2-KO小鼠心脏在缺血/再灌注后功能恢复更好，梗死面积更小。在基线条件下，通过呼吸链活性和生物合成标志物的生化分析以及线粒体超微结构的电子显微镜研究表明，Lcn2-KO心脏的线粒体功能显著增强。急性或慢性给予脂联素-2会损害Lcn2-KO小鼠心脏对缺血/再灌注的功能恢复，并抑制线粒体功能。这些效应与细胞内磷脂脂肪酸酰基链组成的广泛改变有关。例如，脂联素-2促进了亚油酸（C18:2）在不同类型磷脂之间的重新分布，包括心磷脂，一种主要位于线粒体内膜的结构独特的磷脂。
缺乏脂联素-2可改善离体小鼠心脏缺血/再灌注后的功能恢复，这与线粒体功能的恢复和磷脂重塑有关。
