title: Improved functional recovery to I/R injury in hearts from lipocalin-2 deficiency mice: restoration of mitochondrial function and phospholipids remodeling.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Fan
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Karen Sl
authors.initials: KS
authors.lastname: Lam
authors.forename: Thorsten
authors.initials: T
authors.lastname: Berger
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.forename: Jessie Ws
authors.initials: JW
authors.lastname: Yue
authors.forename: Erfei
authors.initials: E
authors.lastname: Song
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
authors.forename: Gary
authors.initials: G
authors.lastname: Sweeney
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang