SEARCH · PubMed Health

Results for “LOX”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

PubMed2003

Structural and functional diversity of lysyl oxidase and the LOX-like proteins.

Lysyl oxidase (LOX) and four lysyl oxidase-like proteins, LOXL, LOXL2, LOXL3 and LOXL4, each contain a copper binding site, conserved lysyl and tyrosyl residues that may contribute to quinone co-factor formation, and a cytokine receptor-like domain. Each protein differs mainly in their N-terminal sequence, which may confer individual functions. Processing of the LOX proteins by BMP-1 and possibly other mechanisms may result in multiple functional forms. Splicing, reported for LOXL3, may also generate additional variants with unique functions. Each LOX, with its individual, developmentally regulated tissue and cell-specific expression and localization, results in a complex structural and functional variation for the LOX amine oxidases. The presence of only two LOX-like proteins in Drosophila, each with distinct spatial and temporal expression, allows for the assignment of individual function to one of these amine oxidases. Comparative expression analysis of each LOX protein is presented to help determine their functional significance.

Amino Acid Oxidoreductases↗

PubMed2000

A cre-lox recombination system for the targeted integration of circular yeast artificial chromosomes into embryonic stem cells.

The ability to produce embryonic stem (ES) cell lines containing different yeast artificial chromosomes (YACs) integrated into the same location in the genome provides a system for comparing the bio-logical effects of YAC transgenes without the confounding influences of integration site and copy number. A targeting system was developed for the directed integration of circular YACs into mouse ES cells. The system combines Cre-lox recombination technology, specifically a positive-selection integration system, with circular YAC lipofection technology to achieve single copy targeted integration of a transgene. Three independent germline competent ES cell lines [lox-containing ES lines (designated LES)] were created that contain a '-neo-lox' cassette integrated at different sites within the ES genome. A plasmid containing YAC vector sequences and a complementary '-neo-lox' cassette was used to circularize two linear YACs containing genomic DNA from human chromosome 21. The circularized YACs were then targeted to the lox sites of the LES cell lines. Polymerase chain reaction and Southern analysis demonstrated that 21% (5 of 24) of lox-recombinants contain a full-length intact YAC. This system will make the study of YAC transgenic mice more reliable and reproducible, allowing the potential for direct comparison of different transgenes expressed from the same site within the genome.

Animals↗

PubMed2004

Betaxolol stimulates eNOS production associated with LOX-1 and VEGF in Dahl salt-sensitive rats.

OBJECTIVE: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and vascular endothelial growth factor (VEGF) may play key roles in atherosclerosis, and have been shown to regulate nitric oxide (NO) production. However, the molecular mechanisms by which betaxolol, a specific beta 1-antagonist, stimulates endothelial NO synthase (eNOS) expression associated with LOX-1 and VEGF are unclear. We hypothesized that in the left ventricle of Dahl salt-sensitive (DS) rats, betaxolol reduces production of LOX-1 by suppressing NAD(P)H oxidase p47phox expression; betaxolol stimulates eNOS production associated with expression of VEGF and LOX-1; and betaxolol inhibits adhesion molecule and signal transduction, which may be involved in cardiovascular remodeling. METHODS: After 5 weeks of feeding an 8% NaCl diet to 6-week-old DS rats (i.e. at 11 weeks of age), a distinct stage of concentric left ventricular hypertrophy was noted. Betaxolol (0.9 mg/kg per day) was administered to 6-week-old DS rats for 5 weeks until the onset of left ventricular hypertrophy stage. RESULTS: Decreased expression of eNOS and VEGF in DS rats was increased by betaxolol. Upregulated LOX-1, NAD(P)H oxidase p47phox, intercellular and vascular cell adhesion molecule-1 expression and phosphorylations of p38 mitogen-activated protein kinase and p65 nuclear factor-kappa B activity were inhibited by betaxolol. Betaxolol administration resulted in significant improvement of cardiovascular remodeling and suppression of transforming growth factor-beta 1 and type I collagen expression. CONCLUSIONS: These results suggest that cardioprotective effects of betaxolol may stimulate eNOS production associated with VEGF and LOX-1, and inhibit adhesion molecule and signal transduction in DS rats.

Animals↗

PubMed2006

Cre-lox-based system for multiple gene deletions and selectable-marker removal in Lactobacillus plantarum.

The classic strategy to achieve gene deletion variants is based on double-crossover integration of nonreplicating vectors into the genome. In addition, recombination systems such as Cre-lox have been used extensively, mainly for eukaryotic organisms. This study presents the construction of a Cre-lox-based system for multiple gene deletions in Lactobacillus plantarum that could be adapted for use on gram-positive bacteria. First, an effective mutagenesis vector (pNZ5319) was constructed that allows direct cloning of blunt-end PCR products representing homologous recombination target regions. Using this mutagenesis vector, double-crossover gene replacement mutants could be readily selected based on their antibiotic resistance phenotype. In the resulting mutants, the target gene is replaced by a lox66-P(32)-cat-lox71 cassette, where lox66 and lox71 are mutant variants of loxP and P(32)-cat is a chloramphenicol resistance cassette. The lox sites serve as recognition sites for the Cre enzyme, a protein that belongs to the integrase family of site-specific recombinases. Thus, transient Cre recombinase expression in double-crossover mutants leads to recombination of the lox66-P(32)-cat-lox71 cassette into a double-mutant loxP site, called lox72, which displays strongly reduced recognition by Cre. The effectiveness of the Cre-lox-based strategy for multiple gene deletions was demonstrated by construction of both single and double gene deletions at the melA and bsh1 loci on the chromosome of the gram-positive model organism Lactobacillus plantarum WCFS1. Furthermore, the efficiency of the Cre-lox-based system in multiple gene replacements was determined by successive mutagenesis of the genetically closely linked loci melA and lacS2 in L. plantarum WCFS1. The fact that 99.4% of the clones that were analyzed had undergone correct Cre-lox resolution emphasizes the suitability of the system described here for multiple gene replacement and deletion strategies in a single genetic background.

Gene Deletion↗

PubMed2005

New multiple-deletion method for the Corynebacterium glutamicum genome, using a mutant lox sequence.

Due to the difficulty of multiple deletions using the Cre/loxP system, a simple, markerless multiple-deletion method based on a Cre/mutant lox system combining a right-element (RE) mutant lox site with a left-element (LE) mutant lox site was employed for large-scale genome rearrangements in Corynebacterium glutamicum. Eight distinct genomic regions that had been identified previously by comparative analysis of C. glutamicum R and C. glutamicum 13032 genomes were targeted for deletion. By homologous recombination, LE and RE mutant lox sites were integrated at each end of a target region. Highly efficient and accurate deletions between the two chromosomal mutant lox sites in the presence of Cre recombinase were realized. A deletion mutant lacking 190 kb of chromosomal regions, encoding a total of 188 open reading frames (ORFs), was obtained. These deletions represent the largest genomic excisions in C. glutamicum reported to date. Despite the loss of numerous predicted ORFs, the mutant exhibited normal growth under standard laboratory conditions. The Cre/loxP system using a pair of mutant lox sites provides a new, efficient genome rearrangement technique for C. glutamicum. It should facilitate the understanding of genome functions of microorganisms.

Base Sequence↗

PubMed2004

Asymmetric dimethylarginine upregulates LOX-1 in activated macrophages: role in foam cell formation.

Intimal infiltration by monocytes and accumulation of lipids represent a critical step in the formation of fatty streaks during atherogenesis. Because elevated plasma levels of asymmetric dimethylarginine (ADMA), a potent nitric oxide (NO) synthase (NOS) inhibitor, are prevalent in diverse cardiovascular diseases, the goal of this study was to examine the contribution of NO deficiency to macrophage lipid accumulation. Inhibition of NO synthesis in PMA-primed human monocytic leukemia HL-60 cells resulted in a twofold increase in expression of the receptor for oxidized LDL (OxLDL), termed the lectin-like OxLDL receptor (LOX-1). Blockade of inducible NOS in activated macrophages resulted in 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-OxLDL accumulation and imparted macrophages with a foamy appearance as detected with oil-red O lipid staining. ADMA (15 microM) or N(G)-nitro-l-arginine methyl ester (l-NAME, 300 microM), both of which suppress inducible NOS activity, increased oil-red staining 1.9- and 2.8-fold, respectively. Macrophages treated with ADMA or l-NAME showed a 2.4-fold increase in accumulation of DiI-OxLDL. To examine the role of LOX-1 in this process, we used small interfering RNA (siRNA) duplex-mediated LOX-1 gene silencing. LOX-1 expression was suppressed twofold by siRNA as shown by Western blot analysis. This suppression was associated with a two- to fourfold decrease in DiI-OxLDL uptake as identified by fluorescence microscopy and decreased oil-red O staining by activated macrophages. In conclusion, accumulation of ADMA (a competitive inhibitor of NOS) in patients with chronic renal failure may be responsible for upregulation of LOX-1 receptor and increased OxLDL uptake, thus contributing to lipidosis and foam cell formation. The data illustrate an additional nonendothelial mode of antiatherogenic action of NO: prevention of LOX-1 induction and lipid accumulation by macrophages.

Arginine↗

PubMed2006

Molecular dissection of angiotensin II-activated human LOX-1 promoter.

OBJECTIVE: LOX-1, a receptor for oxidized low-density lipoprotein, plays a critical role in atherosclerosis. Its expression is upregulated by pro-atherogenic stimuli, such as angiotensin II (Ang II). In this study, we explored LOX-1 transcriptional promoter activation in response to Ang II in human coronary artery endothelial cells (HCAECs). METHODS AND RESULTS: We constructed full-length and deletion LOX-1 promoter mutants and examined their activation in response to Ang II in HCAECs. The Ang II (1 micromol/L for 24 hours) markedly induced LOX-1 promoter activity beyond the basal level, and a 116-bp fragment (between nt -2247 and -2131) was necessary for this induction. Within this 116-bp promoter fragment, there is a potential binding motif for transcription factor NF-kappaB. By EMSA, we observed the activation of NF-kappaB by Ang II. The critical role of NF-kappaB in Ang II-induced LOX-1 promoter activation was confirmed by mutagenesis assay, and further confirmed by blocking NF-kappaB activation with the NF-kappaB inhibitor caffeic acid phenethyl ester or NF-kappaB p65 siRNA. CONCLUSIONS: This study strongly suggests that Ang II, by activating NF-kappaB, induces LOX-1 promoter activation.

Angiotensin II↗

PubMed2003

LOX-1 mediates oxidized low-density lipoprotein-induced expression of matrix metalloproteinases in human coronary artery endothelial cells.

BACKGROUND: Oxidized LDL (ox-LDL) accumulation in the atherosclerotic region may enhance plaque instability. Both accumulation of ox-LDL and expression of its lectin-like receptor, LOX-1, have been shown in atherosclerotic regions. This study was designed to examine the role of LOX-1 in the modulation of metalloproteinases (MMP-1 and MMP-3) in human coronary artery endothelial cells (HCAECs). METHODS AND RESULTS: HCAECs were incubated with ox-LDL (10 to 80 micro g/mL) for 1 to 24 hours. Ox-LDL increased the expression of MMP-1 (collagenase) and MMP-3 (stromelysin-1) in a concentration- and time-dependent manner. Ox-LDL also increased collagenase activity. Ox-LDL did not significantly affect the expression of tissue inhibitors of metalloproteinases. Native LDL had no effect on the expression of MMPs. The effects of ox-LDL were mediated by its endothelial receptor, LOX-1, because pretreatment of HCAECs with a blocking antibody to LOX-1 (JTX92, 10 micro g/mL) prevented the expression of MMPs in response to ox-LDL (P<0.01). In parallel experiments, ox-LDL caused the activation of protein kinase C (PKC), which was inhibited by LOX-1 antibody. The PKC-beta isoform played a critical role in the expression of MMPs, because the PKC-beta inhibitor hispidin reduced ox-LDL-induced activation of PKC and the expression of MMPs. Other PKC subunits (alpha, gamma, and epsilon) did not affect the expression of MMPs. CONCLUSIONS: These findings indicate that ox-LDL, via LOX-1 activation, modulates the expression and activity of MMPs in HCAECs. In this process, activation of the PKC-beta subunit plays an important signaling role.

Cells, Cultured↗

PubMed1999

Structure and chromosomal assignment of the human lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) gene.

We have reported the cDNA cloning of a modified low-density-lipoprotein (LDL) receptor, designated lectin-like oxidized LDL receptor-1 (LOX-1), which is postulated to be involved in endothelial dysfunction and the pathogenesis of atherosclerosis. Here, we determined the organization of the human LOX-1 gene, including the 5'-regulatory region. The 5'-regulatory region contained several potential cis-regulatory elements, such as GATA-2 binding element, c-ets-1 binding element, 12-O-tetradecanoylphorbol 13-acetate-responsive element and shear-stress-responsive elements, which may mediate the endothelium-specific and inducible expression of LOX-1. The major transcription-initiation site was found to be located 29 nucleotides downstream of the TATA box and 61 nucleotides upstream from the translation-initiation codon. The minor initiation site was found to be 5 bp downstream from the major site. Most of the promoter activity of the LOX-1 gene was ascribed to the region (-150 to -90) containing the GC and CAAT boxes. The coding sequence was divided into 6 exons by 5 introns. The first 3 exons corresponded to the different functional domains of the protein (cytoplasmic, transmembrane and neck domains), and the residual 3 exons encoded the carbohydrate-recognition domain similar to the case of other C-type lectin genes. The LOX-1 gene was a single-copy gene and assigned to the p12.3-p13.2 region of chromosome 12. Since the locus for a familial hypertension has been mapped to the overlapping region, LOX-1 might be the gene responsible for the hypertension.

Base Sequence↗

PubMed2002

Expression analysis of recombinant lysyl oxidase (LOX) in myofibroblastlike cells.

Lysyl oxidase (LOX), originally known as the enzyme required for initiation of covalent cross-linking in collagens and elastin, is now known to be a member of a family of genetically related proteins. LOX, or a related protein, has also been localized intracellularly, both in association with the cytoskeleton and in the cell nucleus. To determine the structural requirements for secretion, maturation, and nuclear location of LOX in a cellular context, we have devised an homologous cell model for expression of the recombinant protein. Murine recombinant LOX was expressed in 3T6-5 myofibroblast-like cells as a 51-kD precursor, which was observed in the cytoplasm but not in the nucleus. To investigate whether potential alternative translation initiation sites were involved in specifying a nuclear form of LOX, constructs mutated or deleted for ATG(+1) were used, but alternative initiation at CTG(-315) or ATG(+418) did not lead to the expression of intranuclear forms. Residues 23 to 157 of the proregion were essential for export of the precursor, while mutation of the putative site for maturation by procollagen C-proteinase abolished processing to the mature form of the enzyme. Cross-linking of collagen, as measured by pyridinoline analysis, increased twofold with the recombinant cells, compared to non-transfected controls. This shows the specific contribution of LOX, as opposed to other genetic forms of the enzyme, to cross-linking in a cellular context.

Amino Acids↗

PubMed2006

[Lox-1--an actor in cardiovascular disease?].

BACKGROUND: Among risk factors such as smoking, hypertension and LDL cholesterol, oxidized LDL (ox-LDL) has emerged as a new and interesting factor. Scavenger receptors are a group of cell-surface receptors located on various cell types within the vessel wall with special affinity for ox-LDL. Of all the scavenger receptors involved in coronary heart disease, the lectin-like oxidized low-density lipoprotein receptor (LOX-1) is probably the most important. MATERIAL AND METHODS: This article provides a general overview of the scavenger receptors, with special emphasis on LOX-1 and its role in hypertension, heart failure, atherosclerotic heart disease and diabetes mellitus, based on the literature and our own published data. RESULTS AND INTERPRETATION: LOX-1 is located in various cell types within atherosclerotic plaque, in humans as well in animals, and it accumulates during the progression of the plaque. The receptor is highly expressed in hypertension, hyperhomocysteinaemia and diabetes mellitus. Data indicate that there is a complex interaction between LOX-1 and a number of different processes, such as inflammation, lipid accumulation and oxidative stress. In addition, LOX-1 seems to have therapeutic potential, and a prospective treatment aiming to reduce the level of LOX-1 may be important in the development of atherosclerotic disease, such as coronary heart disease.

Biomarkers↗

PubMed1997

Enhanced expression of endothelial oxidized low-density lipoprotein receptor (LOX-1) in hypertensive rats.

Oxidized low-density lipoprotein (Ox-LDL) has been implicated in the attenuated endothelium-dependent vasodilatation in atherosclerotic arteries and, possibly, in hypertension. The aim of the present study was to investigate gene expression of recently-identified endothelial Ox-LDL receptor (LOX-1) in hypertensive state. SHR-SP, WKY, Dahl salt-sensitive (DS) and salt-resistant rats (DR) were fed salt-loaded or control diet. RNA was extracted from the aorta and vein. LOX-1 expression was examined by Northern blotting. LOX-1 mRNA was low in the aorta and vein of WKY, whereas it was markedly upregulated in those of SHR-SP. LOX-1 expression was low in the aorta of DR on both diets and of DS on a control diet, whereas it was elevated in that of salt-loaded DS. These results indicated that LOX-1 expression in the aorta and vein was upregulated in hypertensive rats, which may be involved in the impaired endothelium-dependent vasodilation in these rats.

Animals↗

PubMed2001

Inhibition of LOX-1 by statins may relate to upregulation of eNOS.

LOX-1, a receptor for oxidized low-density lipoprotein (ox-LDL), plays a critical role in endothelial dysfunction and atherosclerosis; both of these conditions are associated with diminished expression of constitutive endothelial nitric oxide synthase (eNOS). Recent studies show that HMG CoA reductase inhibitors (statins) exert cardioprotective effect. We examined the role of LOX-1 in eNOS expression and modulation of this relationship by two different statins, simvastatin and atorvastatin in human coronary artery endothelial cells (HCAECs). Ox-LDL (40 microg/ml) upregulated the expression of LOX-1; simultaneously, there was a reduction in eNOS expression. Pretreatment of HCAECs with simvastatin or atorvastatin (1 and 10 microM) reduced ox-LDL-induced upregulation of LOX-1 and downregulation of eNOS (both P < 0.05). High concentration of statins (10 microM) was more potent than the low concentration (1 microM) (P < 0.05). Both statins also attenuated ox-LDL-mediated activation of MAP kinase. These observations indicate that statins attenuate the effect of ox-LDL on eNOS expression. Inhibitory effect on LOX-1 and subsequently MAP kinase activity provides a potential mechanism of beneficial effects of statins beyond lowering cholesterol.

Atorvastatin↗

PubMed2002

Cre/ lox site-specific recombination controls the excision of a transgene from the rice genome.

The Cre/ lox site-specific recombination controls the excision of a target DNA segment by recombination between two loxsites flanking it, mediated by the Cre recombinase. We have studied the functional expression of the Cre/ lox system to excise a transgene from the rice genome. We developed transgenic plants carrying the target gene, hygromycin phosphotransferase ( hpt) flanked by two lox sites and transgenic plants harboring the Cre gene. Each lox plant was crossed with each Cre plant reciprocally. In the Cre /lox hybrid plants, the Cre recombinase mediates recombination between two lox sites, resulting in excision of the hpt gene. The recombination event could be detected because it places the CaMV 35S promoter of the hpt gene adjacent to a promoterless gusA gene; as a result the gusA gene is activated and its expression could be visualized. In 73 Cre /lox hybrid plants from various crosses of T0 transgenic plants, 19 expressed GUS, and in 132 Cre /lox hybrid plants from crosses of T2 transgenic plants, 77 showed GUS expression. Molecular data proved the excision event occurred in all the GUS(+) plants. Recombination occurred with high efficiency at the early germinal stage, or randomly during somatic development stages.

Journal Article↗

PubMed2004

Aspirin inhibits ox-LDL-mediated LOX-1 expression and metalloproteinase-1 in human coronary endothelial cells.

BACKGROUND: Aspirin is thought to exert salutary effects in vascular disease states by inhibiting platelet aggregation. Endothelial activation, accumulation of oxidized low-density lipoprotein (ox-LDL) and intense inflammation also characterize atherosclerotic plaque in acute myocardial ischemia. Ox-LDL induces expression of lectin-like receptors (LOX-1) on endothelial cells and leads to the expression of matrix metalloproteinases (MMPs), which destabilize the atherosclerotic plaque. We hypothesized that aspirin may interfere with LOX-1 expression and subsequent MMP activation. METHODS AND RESULTS: Cultured human coronary artery endothelial cells (HCAECs) were incubated with aspirin (1-5 mM), sodium salicylate (5 mM) or the cyclo-oxygenase inhibitor indomethacin (0.25 mM) before treatment with ox-LDL. Aspirin, in a dose- and time-dependent fashion, reduced ox-LDL-mediated LOX-1 expression (P<0.01). Ox-LDL also increased MMP-1 expression and activity, and treatment of HCAECs with aspirin decreased this effect (P<0.01). Ox-LDL also enhanced the activity of p38MAPK in HCAECs, and aspirin blocked this effect of ox-LDL (P<0.01). Treatment of HCAECs with salicylate, but not indomethacin, resulted in a suppression of LOX-1 expression, an effect similar to that of aspirin. Importantly, both aspirin and salicylate, but not indomethacin, decreased superoxide anion generation in ox-LDL-treated HCAECs (P<0.05). CONCLUSION: These observations suggest that aspirin inhibits ox-LDL-mediated LOX-1 expression and interferes with the effects of ox-LDL in intracellular signaling (p38MAPK activation) and subsequent MMP-1 activity. These novel effects of aspirin may complement its platelet inhibitory effect in acute myocardial ischemia.

Anions↗

PubMed2005

Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1): a critical player in the development of atherosclerosis and related disorders.

LOX-1, a lectin-like 52-kD receptor for oxidized low-density lipoproteins (ox-LDL), is present primarily on endothelial cells. This receptor is upregulated by ox-LDL itself and by angiotensin II, endothelin, cytokines, and shear stress, all participants in atherosclerosis. This receptor is upregulated in the arteries of hypertensive, dyslipidemic, and diabetic animals. Upregulation of LOX-1 has been identified in atherosclerotic arteries of several animal species and humans, not only on the endothelial lining, but also in the neovasculature of the atherosclerotic plaque, and this receptor is often co-localized with apoptotic cells. Recent studies show upregulation of LOX-1 in the ischemic-reperfused myocardium. LOX-1 inhibition is associated with attenuation of atherosclerosis and associated ischemic injury. LOX-1 may be a novel, exciting target for drug therapy.

Apoptosis↗

PubMed2004

Synthesis and biological evaluation of new phenidone analogues as potential dual cyclooxygenase (COX-1 and COX-2) and human lipoxygenase (5-LOX) inhibitors.

A new series of potential human 5-LOX inhibitors structurally related to the 1-phenyl-3-pyrazolidinone (phenidone, 2) has been synthesized and the activity against COX-1, COX-2, and human 5-LOX enzymes has been evaluated. In contrast with literature data, we observed that phenidone resulted to be inactive against human 5-LOX, while retains its activity against cyclooxygenases in a micromolar range. The present results suggest that the substitution of the amino function at the 4-position is detrimental in terms of activity toward COX-1 and COX-2, while the presence of a double bond at the 4,5-position does not alter the biological profile against COX. The absence of activity vs. human 5-LOX strongly suggests a re-consideration of phenidone and its analogs as 5-LOX inhibitors in humans.

Cyclooxygenase Inhibitors↗

PubMed2006

Lectin-like oxidized-LDL receptor-1 (LOX-1) polymorphisms influence cardiovascular events rate during statin treatment.

BACKGROUND: Oxidized-LDL (ox-LDL) are involved in atherothrombosis by induction of endothelial dysfunction and thrombosis. The specific receptor lectin-like oxidized-LDL receptor-1 (LOX-1) is expressed in endothelial cells, monocytes and platelets. LOX-1 gene allelic variants (3'UTR/T) have been related with cardiovascular events and reduced anti-platelet activity induced by statins. OBJECTIVES: To detect whether LOX-1 polymorphisms could affect statins effectiveness in cardiovascular prevention. PATIENTS/METHODS: The present was a retrospective study performed in 751 white hypercholesterolemic subjects treated with increasing doses of atorvastatin (n=382, 247 male, 135 female) or simvastatin (n=369, 244 male, 125 female) up to 4 years, whose LDL target was 3.36 mmol/L according to the National Cholesterol Education Program, Adult Treatment Panel III (NCEP-ATPIII). Single nucleotide polymorphism were evaluated by allelic discrimination assays (PCR), lipid profile by enzymatic-colorimetric methods and C-reactive protein (CRP) by a nephelometric technique. RESULTS: Twenty-three non-ST elevation (NSTEMI) and eleven ST-elevation myocardial infarction (STEMI) were encountered in the observational period without differences between treatments (p=0.175) and sex (p=0.139). Each symptomatic subject (10 reaching the appropriate LDL target and 24 with still undesirable LDL) had the 3'UTR/T allelic variant (adjusted O.R. 4.63, 95% C.I. 3.46-6.70, p<0.0001). Among patients not reaching LDL target the C allele resulted protective with respect to T carriers (p<0.00001). Also, similar changes of CRP resulted in different event rate between T and C carriers (p<0.001) in the whole cohort. CONCLUSIONS: In the studied population LOX-1 genetic variants influence cardiovascular risk reduction induced by statins also in patients not reaching the LDL target. The previously described LOX-1-related antithrombotic actions of both statins employed could have a specific role in what observed, suggesting a genetic influence in statins LDL-lowering partially related actions.

Aged↗