| AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Am J Transl Res 2012;4(1):60-71
Original Article
Improved functional recovery to I/R injury in hearts from lipocalin-2
deficiency mice: restoration of mitochondrial function and
phospholipids remodeling
Bo Yang, Pengcheng Fan, Aimin Xu, Karen SL Lam, Thorsten Berger, Tak W Mak, Hung-Fat Tse, Jessie WS Yue,
Erfei Song, Paul M Vanhoutte, Gary Sweeney, Yu Wang
Department of Pharmacology and Pharmacy, Department of Medicine and Research Center of Heart, Brain,
Hormone, and Healthy Aging, the University of Hong Kong, Hong Kong, China; the Campbell Family Institute for
Breast Cancer Research, Princess Margaret Hospital and Department of Biology, York University, Toronto,
Ontario, Canada.
Received November 17, 2011; accepted December 3, 2011; Epub January 5, 2012; Published January 15, 2012
Abstract: Aims- 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
pathophysiological 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. Methods and 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. (AJTR1111003).
Keywords: Lipocalin-2, adipokine, heart, mitochondria, phospholipids
Full Text PDF
Address all correspondence to:
Dr. Yu Wang
Level 2, Laboratory Block
21 Sassoon Road, Pokfulam
Hong Kong, China.
Tel: 852 28192864 Fax: 852 28170859.
E-mail yuwanghk@hku.hk.
Original Article
Improved functional recovery to I/R injury in hearts from lipocalin-2
deficiency mice: restoration of mitochondrial function and
phospholipids remodeling
Bo Yang, Pengcheng Fan, Aimin Xu, Karen SL Lam, Thorsten Berger, Tak W Mak, Hung-Fat Tse, Jessie WS Yue,
Erfei Song, Paul M Vanhoutte, Gary Sweeney, Yu Wang
Department of Pharmacology and Pharmacy, Department of Medicine and Research Center of Heart, Brain,
Hormone, and Healthy Aging, the University of Hong Kong, Hong Kong, China; the Campbell Family Institute for
Breast Cancer Research, Princess Margaret Hospital and Department of Biology, York University, Toronto,
Ontario, Canada.
Received November 17, 2011; accepted December 3, 2011; Epub January 5, 2012; Published January 15, 2012
Abstract: Aims- 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
pathophysiological 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. Methods and 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. (AJTR1111003).
Keywords: Lipocalin-2, adipokine, heart, mitochondria, phospholipids
Full Text PDF
Address all correspondence to:
Dr. Yu Wang
Level 2, Laboratory Block
21 Sassoon Road, Pokfulam
Hong Kong, China.
Tel: 852 28192864 Fax: 852 28170859.
E-mail yuwanghk@hku.hk.
 | |  | |  | |  | |  | |  | |  |