LOX-1/LOXIN: The Yin/Yang of Atheroscleorosis

Atherosclerosis is the first cause of death in industrialized countries. Together with traditional risk factors (male gender, hypercholesterolemia, hypertension, diabetes, smoking and age), non-traditional risk factors have also been described as predisposing to this disease. Among these, oxidized l...

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Bibliographic Details
Published in:Cardiovascular drugs and therapy 2011-10, Vol.25 (5), p.489-494
Main Authors: Mango, Ruggiero, Predazzi, Irene Marta, Romeo, Francesco, Novelli, Giuseppe
Format: Article
Language:English
Subjects:
Animals
Atherosclerosis - genetics
Atherosclerosis - metabolism
Cardiology
Humans
Lipoproteins, LDL - metabolism
Medicine
Medicine & Public Health
Polymorphism, Single Nucleotide
Protein Isoforms
Scavenger Receptors, Class E - genetics
Scavenger Receptors, Class E - metabolism
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Summary:Atherosclerosis is the first cause of death in industrialized countries. Together with traditional risk factors (male gender, hypercholesterolemia, hypertension, diabetes, smoking and age), non-traditional risk factors have also been described as predisposing to this disease. Among these, oxidized low density lipoproteins (OxLDL) have been described in correlation to many proatherogenic processes. Many of the effects of OxLDL are mediated by the lectin like oxidized low density lipoprotein receptor 1 (LOX-1), expressed on endothelial cells, macrophages, SMCs and platelets. LOX-1 is encoded by the lectin like oxidized low density lipoprotein receptor 1 ( OLR1 ) gene, located in the p12.3–p13.2 region of human chromosome 12. Variations on this gene have been studied extensively both at the functional and epidemiological level. Despite the fact that functional roles for two variants have been demonstrated, the epidemiological studies have provided inconsistent and inconclusive results. Of particular interest, it has been demonstrated that a linkage disequilibirum block of SNPs located in the intronic sequence of the OLR1 gene modulates the alternative splicing of OLR1 mRNA, leading to different ratios of LOX-1 full receptor and LOXIN, an isoform lacking part of the functional domain. As demonstrated, LOXIN acts by blocking the negative effective of LOX-1 activation. Here we review the state of the art regarding LOX-1, LOXIN, and the functional effects that are associated with the interaction of these molecules.
ISSN:0920-3206
1573-7241
DOI:10.1007/s10557-011-6333-5