Expression of lectin-like oxidized low-density lipoprotein receptors during ischemia-reperfusion and its role in determination of apoptosis and left ventricular dysfunction.
OBJECTIVE
The goal of this study was to determine the role of lectin-like oxidized low-density lipoprotein receptors (LOX-1), a recently identified oxidized low-density lipoprotein (ox-LDL) receptor, in ischemia-reperfusion injury to the heart.


BACKGROUND
Reactive oxygen species (ROS) released during ischemia-reperfusion oxidize low-density lipoproteins; LOX-1 is upregulated by ox-LDL and ROS, and is involved in cell injury.


METHODS
Anesthetized rats were subjected to left coronary artery ligation for 60 min (n = 10, ischemia group), or ischemia followed by 60 min of reperfusion (n = 30, ischemia-reperfusion group). Rats in the latter group were treated with saline, the LOX-1 blocking antibody JXT21 (10 mg/kg), or nonspecific anti-goat immunoglobulin G (IgG) (10 mg/kg). Ten other rats underwent thoracotomy without coronary ligation (sham control).


RESULTS
Ischemia-reperfusion was associated with an increase in LOX-1 expression, lipid peroxidation and apoptosis, a large infarct area, and a decrease in left ventricular function (all, p < 0.01 vs. sham control and ischemia alone groups). Treatment of rats with LOX-1 antibody prevented ischemia-reperfusion-induced upregulation of LOX-1. Importantly, the LOX-1 antibody reduced apoptosis by 48%, lipid peroxidation by 39%, and myocardial infarct size by 45%, and improved left ventricular function (first derivative of pressure measured over time: -47% to -18%, p < 0.01). Nonspecific IgG had no effect.


CONCLUSIONS
Lectin-like oxidized low-density lipoprotein receptors are upregulated during myocardial ischemia-reperfusion, and appear to be associated with apoptosis, necrosis, and left ventricular functional deterioration.
Li
Dayuan
D
Departments of Internal Medicine, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA.
Williams
Victor
V
Liu
Ling
L
Chen
Hongjiang
H
Sawamura
Tatsuya
T
Romeo
Francesco
F
Mehta
Jawahar L
JL
D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000235:genetics* / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000235:genetics* / Q000502:physiology*; D051131:Receptors, Oxidized LDL; D015427:Reperfusion Injury / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D051127:Scavenger Receptors, Class E; D018487:Ventricular Dysfunction, Left / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*
C495136:OLR1 protein, rat; C495138:Olr1 protein, mouse; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E