LOX-1 mediates vascular lipid retention under hypertensive state.
OBJECTIVE
Hypertension is a powerful independent risk factor for atherosclerotic cardiovascular diseases; however, the precise molecular mechanisms whereby hypertension promotes atherosclerotic formation remain to be determined. The interaction between oxidized low-density lipoprotein (oxLDL) and its receptor lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays a critical role in atherogenesis. To clarify how hypertension promotes atherosclerosis, we investigated specific roles of LOX-1 in acceleration of lipid deposition under a hypertensive state.


METHODS
We employed a model of stroke-prone spontaneously hypertensive rats (SHR-SP) that exhibits acute lipid deposition in mesenteric artery induced by high fat and salt loading. These vascular lipid deposition lesions share similar characteristics with the initial lesions of human atherosclerosis.


RESULTS
The enhanced LOX-1 expression in SHR-SP was associated with oxidized LDL deposited in vascular wall. Anti-LOX-1 neutralizing antibody dramatically suppressed the lipid deposition in vivo in SHR-SP. Vitamin E decreased serum oxLDL-like LOX-1 ligands, and suppressed the vascular lipid deposition. The vascular permeability, evaluated by the leakage of Evans blue, was markedly enhanced by pretreatment of oxLDL. The enhancement of vascular permeability induced by oxLDL was suppressed by anti-LOX-1 antibody.


CONCLUSIONS
The enhanced expression and activation of LOX-1 mediated the enhancement of vascular permeability, which contributed to the vascular lipid accumulation under hypertensive states.
Nakano
Atushi
A
Department of Vascular Physiology, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
Inoue
Nobutaka
N
Sato
Yuko
Y
Nishimichi
Norihisa
N
Takikawa
Kenji
K
Fujita
Yoshiko
Y
Kakino
Akemi
A
Otsui
Kazunori
K
Yamaguchi
Saburo
S
Matsuda
Haruo
H
Sawamura
Tatsuya
T
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E / Q000502:physiology*
C495136:OLR1 protein, rat; D051127:Scavenger Receptors, Class E