Background and Purpose-
oxLDL (
oxidized low-density lipoprotein) has been known for its potential to induce endothelial dysfunction and used as a major serological marker of oxidative stress. Recently, LOX-1 (
lectin-like oxidized low-density lipoprotein receptor-1), a
lectin-like receptor for
oxLDL, has attracted attention in studies of neuronal apoptosis and
stroke. We aim to investigate the impact of LOX-1-deficiency on spontaneous
hypertension-related brain damage in the present study. Methods- We generated a LOX-1 deficient strain on the genetic background of
stroke-prone spontaneously hypertensive rat (SHRSP), an animal model of severe
hypertension and spontaneous
stroke. In this new disease model with
stroke-proneness, we monitored the occurrence of brain abnormalities with and without
salt loading by multiple procedures including T2 weighted magnetic resonance imaging and also explored circulatory
miRNAs as diagnostic
biomarkers for cerebral ischemic injury by microarray analysis. Results- Both T2 weighted magnetic resonance imaging abnormalities and physiological parameter changes could be detected at significantly delayed timing in LOX-1 knockout rats compared with wild-type SHRSP, in either case of normal rat chow and
salt loading (P<0.005 in all instances; n=11-20 for SHRSP and n=13-23 for LOX-1 knockout rats). There were no significant differences in the form of magnetic resonance imaging findings between the strains. A number of
miRNAs expressed in the normal rat plasma, including rno-miR-150-5p and rno-miR-320-3p, showed significant changes after spontaneous brain damage in SHRSP, whereas the corresponding changes were modest or almost unnoticeable in LOX-1 knockout rats. There appeared to be the lessening of correlation of postischemic
miRNA alterations between the injured brain tissue and plasma in LOX-1 knockout rats. Conclusions- Our data show that deficiency of LOX-1 has a protective effect on spontaneous brain damage in a newly generated LOX-1-deficient strain of SHRSP. Further, our analysis of
miRNAs as
biomarkers for ischemic brain damage supports a potential involvement of LOX-1 in blood brain barrier disruption after
cerebral ischemia. Visual Overview- An online visual overview is available for this article.