Copyright © 2007, European Society of Cardiology
LOX-1 deletion alters signals of myocardial remodeling immediately after ischemia–reperfusion
aDepartment of Internal Medicine, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR, USA
bDepartment of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China
cDepartment of Vascular Physiology, National Cardiovascular Center Research Institute, Suita, Osaka, Japan
dChugai Research Institute For Medical Science, Inc., Gotenba, Shizuoka, Japan
eResearch Unit for Functional Genomics, National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan
fDepartment of Developmental and Medical Technology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
*Corresponding author. University of Arkansas for Medical Sciences, 4301 West Markham St., Slot 532, Little Rock, AR 72205-7199, USA. Tel.: +1 501 296 1401; fax: +1 501 686 8319. mehtajl{at}uams.edu
Objective Chronic ischemia is associated with alterations in genes that result in myocardial remodeling. An important biochemical basis of cardiac remodeling is generation of reactive oxygen species (ROS). A few studies have suggested that acute ischemia triggers signals for remodeling. We examined the hypothesis that targeted deletion of lectin-like oxidized-LDL receptor (LOX-1) may inhibit signals related to cardiac remodeling.
Methods and results We generated LOX-1 knockout (KO) mice on C57BL/6 (wild-type mice) background, and subjected wild-type and KO mice to ischemia–reperfusion (I–R). The wild-type mice developed a marked reduction in left ventricular systolic pressure and ±dp/dtmax and an increase in left ventricular end-diastolic pressure following I–R, and this change was much less in the LOX-1 KO mice, indicating preservation of left ventricular function with LOX-1 deletion. There was evidence for marked oxidative stress (NADPH oxidase expression, malondialdehyde and 8-isoprostane) following I–R in the wild-type mice, much less so in the LOX-1 KO mice (P<0.01). In concert, collagen deposition (Masson's trichrome and Picro-sirius red staining) increased dramatically in the wild-type mice, but only half as much in the LOX-1 KO mice (P<0.01). Collagen staining data was corroborated with procollagen-I expression. Further, fibronectin and osteopontin expression increased in the wild-type mice, but to a much smaller extent in the LOX-1 KO mice (P<0.01).
Conclusions These findings provide compelling evidence that LOX-1 is a key modulator of cardiac remodeling which starts immediately following I–R.
KEYWORDS Remodeling; Ischemia; Reperfusion; NADPH oxidase; Extracellular matrix
1 These two authors contributed equally.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Hu, A. Dandapat, L. Sun, M. R. Marwali, N. Inoue, F. Sugawara, K. Inoue, Y. Kawase, K.-i. Jishage, H. Suzuki, et al. Modulation of Angiotensin II-Mediated Hypertension and Cardiac Remodeling by Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Deletion Hypertension, September 1, 2008; 52(3): 556 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hu, A. Dandapat, L. Sun, J. Chen, M. R. Marwali, F. Romeo, T. Sawamura, and J. L. Mehta LOX-1 deletion decreases collagen accumulation in atherosclerotic plaque in low-density lipoprotein receptor knockout mice fed a high-cholesterol diet Cardiovasc Res, July 15, 2008; 79(2): 287 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hu, A. Dandapat, L. Sun, J. A. Khan, Y. Liu, P. L. Hermonat, and J. L. Mehta Regulation of TGF{beta}1-mediated Collagen Formation by LOX-1: Studies Based on Forced Overexpression of TGF{beta}1 in Wild-Type and Lox-1 J. Biol. Chem., April 18, 2008; 283(16): 10226 - 10231. [Abstract] [Full Text] [PDF]
|
|