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Tatsuya Sawamura

Publications and source records attributed to Tatsuya Sawamura.

At least 19 recordsLinked to original sources
PubMed2006

Oxidized LDL binding to LOX-1 upregulates VEGF expression in cultured bovine chondrocytes through activation of PPAR-gamma.

It has been reported that vascular endothelial growth factor (VEGF) and its receptors play an important role in the destruction of articular cartilage in osteoarthritis through increased production of matrix metalloproteinases. We investigated whether the oxidized low-density lipoprotein (ox-LDL) binding to lectin-like ox-LDL receptor-1 (LOX-1) upregulates VEGF expression in cultured bovine articular chondrocytes (BACs). Ox-LDL markedly increased VEGF mRNA expression and protein release in time- and dose-dependent manners, which was significantly suppressed by anti-LOX-1 antibody pretreatment. Activation of peroxisome proliferator-activated receptor (PPAR)-gamma was evident in BACs with ox-LDL addition and was attenuated by anti-LOX-1 antibody. The specific PPAR-gamma inhibitor GW9662 suppressed ox-LDL-induced VEGF expression. These results suggest that the ox-LDL/LOX-1 system upregulates VEGF expression in articular cartilage, at least in part, through activation of PPAR-gamma and supports the hypothesis that ox-LDL is involved in cartilage degradation via LOX-1.

Animals↗
PubMed2006

Dominant-negative lox-1 blocks homodimerization of wild-type lox-1-induced cell proliferation through extracellular signal regulated kinase 1/2 activation.

C-type lectin-like oxidized low-density lipoprotein (Ox-LDL) receptor-1 (Lox-1) belongs to the same family as natural killer cell receptors Ly49A and CD94 and functionally undergoes dimerization. Although Lys262 and Lys263 in the C terminus of bovine (b)Lox-1 play an important role in the uptake of Ox-LDL, mutation of these residues has not been suggested to be a potential source of the dominant-negative property. We hypothesize that dominant-negative human (h)Lox-1 forms a heterodimer with Lox-1-wild-type (WT) and blocks Lox-1-WT-induced cell signaling. Based on the use of molecular imaging techniques with laser scanning confocal microscopy and immunoprecipitation in an hLox-1-expressing Chinese hamster ovary cell system, homodimerization of hLox-1-WT was localized in the cell membrane, and Ox-LDL activated extracellular signal regulated kinase (ERK)1/2 without the translocation of hLox-1-WT. Lys266 and Lys267 of hLox-1, corresponding with Lys262 and Lys263 of bLox-1, were mutated (hLox1-K266A/K267A), and the mutant receptor inhibited hLox-1-WT-induced thymidine incorporation and ERK1/2 activation. Although Ox-LDL binds to the dominant-negative mutant receptor and is taken up by cytoplasm, ERK1/2 activation was blocked by heterodimerization with the mutant receptor and hLox-1-WT in the cell membrane. In addition, in human coronary artery smooth muscle cells, which express hLox-1-WT, we confirmed that the activation of ERK1/2 and [3H]-thymidine incorporation was caused by the addition of Ox-LDL, and these actions were blocked by hLox1-K266A/K267A. In conclusion, the present findings constitute the first evidence that strategies aimed at blocking cell-proliferative pathways at the receptor level could be useful for impairing Lox-1-induced cell proliferation.

Animals↗
PubMed2006

Oxidized low density lipoprotein impairs endothelial progenitor cells by regulation of endothelial nitric oxide synthase.

Oxidized low density lipoprotein (OxLDL) is one of the most important risk factors of cardiovascular disease. Here, we study the impact of OxLDL on endothelial progenitor cells (EPCs) and determine whether OxLDL affects EPCs by an inhibitory effect on endothelial nitric oxide synthase (eNOS). It was found that OxLDL decreased EPC survival and impaired its adhesive, migratory, and tube-formation capacities in a dose-dependent manner. However, all of the detrimental effects of OxLDL were attenuated by pretreatment of EPCs with lectin-like oxidized low density lipoprotein receptor (LOX-1) monoclonal antibody or l-arginine. Western blot analysis revealed that OxLDL dose-dependently decreased Akt phosphorylation and eNOS protein expression and increased LOX-1 protein expression. Furthermore, OxLDL caused a decrease in eNOS mRNA expression and an increase in LOX-1 mRNA expression. These data indicate that OxLDL inhibits EPC survival and impairs its function, and this action is attributable to an inhibitory effect on eNOS.

Apoptosis↗
PubMed2006

LOX-1 scavenger receptor mediates calcium-dependent recognition of phosphatidylserine and apoptotic cells.

The LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) scavenger receptor regulates vascular responses to oxidized-low-density-lipoprotein particles implicated in atherosclerotic plaque formation. LOX-1 is closely related to C-type lectins, but the mechanism of ligand recognition is not known. Here we show that human LOX-1 recognizes a key cellular phospholipid, PS (phosphatidylserine), in a Ca2+-dependent manner, both in vitro and in cultured cells. A recombinant, folded and glycosylated LOX-1 molecule binds PS, but not other phospholipids. LOX-1 recognition of PS was maximal in the presence of millimolar Ca2+ levels. Mg2+ was unable to substitute for Ca2+ in LOX-1 binding to PS, indicating a Ca2+-specific requirement for bivalent cations. LOX-1-mediated recognition of PS-containing apoptotic bodies was dependent on Ca2+ and was decreased to background levels by bivalent-cation chelation, LOX-1-blocking antibodies or PS-containing liposomes. The LOX-1 membrane protein is thus a Ca2+-dependent phospholipid receptor, revealing novel recognition of phospholipids by mammalian lectins.

Animals↗
PubMed2006

Cyclic tensile stretch load and oxidized low density lipoprotein synergistically induce lectin-like oxidized ldl receptor-1 in cultured bovine chondrocytes, resulting in decreased cell viability and proteoglycan synthesis.

Mechanical stimulation is known to be an essential factor in the regulation of cartilage metabolism. We tested the hypothesis that expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) can be modulated by cyclic tensile stretch load in chondrocytes. Cyclic loading of repeated stretch stress at 10 cycles per minute with 10 kPa of stress for 6 h induced expression of LOX-1 to 2.6 times control in cultured bovine articular chondrocytes, equivalent to the addition of 10 microg/mL oxidized low density lipoprotein (ox-LDL) (2.4 times control). Application of the cyclic load to the chondrocytes along with 10 microg/mL ox-LDL resulted in synergistically increased LOX-1 expression to 6.3 times control. Individual application of cyclic loading and 10 microg/mL ox-LDL significantly suppressed chondrocytes viability (84.6% +/- 3.4% and 80.9% +/- 3.2% of control at 24 h, respectively; n = 3; p < 0.05) and proteoglycan synthesis [81.0% +/- 7.1% and 85.7% +/- 5.2% of control at 24 h, respectively; p < 0.05 when compared with 94.6% +/- 4.6% for native-LDL (n = 3)]. Cyclic loading and 10 microg/mL ox-LDL synergistically affected cell viability and proteoglycan synthesis, which were significantly suppressed to 45.6% +/- 4.9% and 48.7% +/- 6.7% of control at 24 h, respectively (n = 3; p < 0.01 when compared with individual application of cyclic loading or 10 microg/mL ox-LDL). In this study, we demonstrated synergistic effects of cyclic tensile stretch load and ox-LDL on cell viability and proteoglycan synthesis in chondrocytes, which may be mediated through enhanced expression of LOX-1 and which has important implications in the progression of cartilage degeneration in osteoarthritis.

Animals↗
PubMed2006

A therapeutic dose of the lipophilic statin pitavastatin enhances oxidant-induced apoptosis in human vascular smooth muscle cells.

We examined effects of a physiologic concentration of pitavastatin (0.01 micromol/L) on oxidant-induced apoptosis in cultured human vascular smooth muscle cells (VSMCs). Apoptosis was induced in VSMCs by hydrogen peroxide (H2O2, 300 micromol/L), as evidenced by in situ nick end-labeling and scanning electron microscopy. This apoptotic response was accompanied by increased activation of mitogen-activated protein kinases (MAPKs--ie, increases in the phosphorylated forms of extracellular signal-regulated kinase (p-ERK), c-Jun N-terminal kinase (p-JNK), and p38 MAPK (p-p38 MAPK). Although pitavastatin alone did not induce VSMC death, pretreatment with pitavastatin significantly enhanced H2O2-induced apoptosis and prolonged activation of JNK and p38 MAPK (for up to 24 h) but not ERK. Expression of MAPK phosphatase-1 (MKP-1) also was upregulated by H2O2, but this was not affected by pitavastatin. The apoptosis accelerating effect was observed also in simvastatin but not in pravastatin. Treating VSMCs with mevalonate, farnesyl pyrophosphate, or geranylgeranyl pyrophosphate completely blocked the statin-induced enhancement of VSMC apoptosis, suggesting that protein prenylation is critically involved. It thus appears that pitavastatin enhances H2O2-induced VSMC apoptosis, at least in part, via increases in MAPK activation and protein prenylation, but independently of MKP-1 expression, which consequently results in reduction of VSMC population.

Apoptosis↗
PubMed2005

Low-density lipoprotein oxidized to various degrees activates ERK1/2 through Lox-1.

Although the standard procedure for preparing extensively oxidized low-density lipoprotein (Ox-LDL) is to incubate it with 10muM CuSO(4) at 37 degrees C for 24h, it is not well known how important the degree of oxidation of LDL is for inducing cell signaling. Since Lox-1 (an Ox-LDL receptor) contributes to cell proliferation through extracellular-signal-regulated kinase (ERK)1/2 activation and subsequently induces plaque growth, we analyzed ERK activity using LDL with various degrees of oxidation, from minimally Ox-LDL, which is mainly in human plasma, to extensively Ox-LDL using capillary electrophoresis (cITP). The cITP was a suitable tool for evaluating the degree of oxidation of LDL for analyzing the optimal conditions for the oxidation of LDL by CuSO(4) to obtain LDL that was oxidized to a degree comparable to that in human plasma. In addition, both minimally and extensively Ox-LDL induced similar levels of ERK1/2 activation through Lox-1 in human coronary artery smooth muscle cells. These results indicate that both minimally and extensively Ox-LDL may be important for the progression of plaque growth through Lox-1. Since most previous reports have provided data only using extensively Ox-LDL, a re-evaluation is needed to analyze several signals that use LDL which has been oxidized to various degrees.

Cell Communication↗
PubMed2005

Oxidized LDL receptor LOX-1 is involved in neointimal hyperplasia after balloon arterial injury in a rat model.

OBJECTIVE: LOX-1 is a multi-ligand receptor originally identified as the endothelial oxidized LDL receptor. LOX-1 expression is also induced in smooth muscle cells in response to proinflammatory and oxidative stimuli. Here, we report on the role of LOX-1 in intimal hyperplasia, in which proinflammatory and oxidative stimuli are increased. METHODS AND RESULTS: Left common carotid artery of rat was injured by a balloon catheter. The expression of LOX-1 was significantly increased within 24 h after the balloon injury and peaked at day 7. LOX-1 expression was observed predominantly in medial smooth muscle cells until day 3, and then shifted to predominantly intimal smooth muscle cells. At day 14, the expression was concentrated in the regenerated endothelial cells. To examine the contributory role of LOX-1 in the growth of intimal smooth muscle cells, rats were administered anti-LOX1 antibody intravenously every 3 days after balloon injury. Anti-LOX-1 antibody administration effectively suppressed intimal hyperplasia, oxidative stress, and leukocyte infiltration compared with control IgG. These findings suggest the importance of LOX-1 expression in the pathogenesis of neointimal formation in conjunction with oxidative stress and leukocyte infiltration. CONCLUSION: The LOX-1 expressed in smooth muscle cells is involved in intimal hyperplasia in a rat model of balloon injury. Manipulation of LOX-1 activity is a novel potential therapeutic target to prevent restenosis after angioplasty.

Animals↗
PubMed2005

Enhanced plasma levels of oxidized low-density lipoprotein increase circulating nuclear factor-kappa B activation in patients with unstable angina.

OBJECTIVES: The purpose of this study was to investigate the effect of circulating levels of oxidized low-density lipoprotein (ox-LDL) on nuclear factor-kappa B (NF-kB) activation in peripheral blood mononuclear cells (PBMC) of patients with unstable angina (UA) or stable angina (SA) and control subjects. BACKGROUND: Nuclear factor-kB might be involved in atherosclerosis, as is suggested by the presence of activated NF-kB in human atherosclerotic lesions. METHODS: Levels of plasma ox-LDL and circulating NF-kB in PBMC (and in separated lymphocytes and monocytes) were measured in 27 control subjects and 29 SA and 27 UA patients. In in vitro studies, the effect of ox-LDL and of the sera derived from a subgroup of UA patients and control subjects on monocytic NF-kB activation was also evaluated. RESULTS: The UA and SA patients had higher levels of circulating ox-LDL and NF-kB in PBMC than control subjects (p < 0.001). The increase in circulating NF-kB was mainly due to the activation of monocytes. In the in vitro studies, ox-LDL dose-dependently increased the activation of NF-kB in monocytes, but not in lymphocytes derived from healthy volunteers. This increase was related to the expression of lectin-like ox-LDL receptor-1 on monocytes. The incubation of monocytes with the sera derived from the UA patients induced a significant increase in NF-kB activation compared with the sera derived from the control subjects. CONCLUSIONS: The data suggest that the activation of NF-kB in monocytes of UA patients is, at least in part, induced by circulating molecules such as ox-LDL, which has been found to be particularly elevated in UA patients.

Aged↗
PubMed2005

Adhesion molecule expression in fibroblasts: alteration in fibroblast biology after transfection with LOX-1 plasmids.

The endothelial lectinlike, oxidatively (ox-) modified LDL receptor LOX-1 is a critical player in the pathogenesis of atherosclerosis and myocardial ischemia. Ox-LDL binding of LOX-1 results in the expression of various adhesion molecules, which attract monocytes to endothelial cells, an initial step in atherogenesis. We wished to examine the role of the ox-LDL/LOX-1 signaling pathway in fibroblasts, which naturally express low levels of LOX-1. Rat cardiac fibroblasts were transfected with either cytomegalovirus (CMV)-LOX-1wt (amino acids [aa] 1 to 273) or CMV-LOX-1(1-261) (an ox-LDL-binding negative mutant, aa 1 to 261) plasmid. Western blots showed that LOX-1 protein expression was increased significantly in cells transfected with CMV-LOX-1wt or CMV-LOX-1(1-261) plasmid (P<0.01 vs control). Fibroblasts transfected with CMV-LOX-1wt showed ox-LDL binding, whereas fibroblasts without transfection and those transfected with CMV-LOX-1(1-261) did not bind ox-LDL. Compared with untransfected cells, ox-LDL treatment (50 microg/mL, 24 hours) markedly induced the expression of the leukocyte adhesion molecules intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM)-1 as well as matrix metalloproteinase (MMP)-1 in cells transfected with CMV-LOX-1wt (P<0.05) but not in cells transfected with CMV-LOX-1(1-261). Concurrently, ox-LDL treatment enhanced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) (P<0.05 vs control) in CMV-LOX-1wt-transfected cells. These data suggest that in cardiac fibroblasts, ox-LDL binds to LOX-1 and activates p38 MAPK, followed by the expression of ICAM-1, VCAM-1, and MMP-1. Thus, fibroblasts transform into an endothelial phenotype on transfection with CMV-LOX-1wt and subsequent exposure to ox-LDL. This study provides a useful model system (plasmid-transfected fibroblasts) to study the molecular biology of LOX-1.

Animals↗
PubMed2005

Overexpression of lectin-like oxidized low-density lipoprotein receptor-1 induces intramyocardial vasculopathy in apolipoprotein E-null mice.

Endothelial dysfunction induced by oxidized low-density lipoprotein (OxLDL) has been implicated in the pathogenesis of atherosclerosis and vasculopathy. Increased expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the receptor for OxLDL in endothelial cells, has been demonstrated in the atherosclerotic plaques from experimental atherosclerotic animal models and human clinical samples. In vitro, activation of LOX-1 alters the expression of several endothelial cell genes that are involved in endothelial dysfunction. To investigate the role of LOX-1 in terms of both endothelial dysfunction and resultant vascular changes, we generated mice overexpressing LOX-1 (LOXtg) in C57BL/6 and apolipoprotein E-null mice (apoEKO) backgrounds. We found that the expression of the transgene was prominent in coronary vessels and cardiomyocytes. The enhancement of OxLDL uptake in LOXtg mice was consistent with the expression level of LOX-1. Under hyperlipidemic conditions, both OxLDL and 8-hydroxy-2'-deoxyguanosine accumulated in the coronary arteries of LOXtg/apoEKO mice. The expression of ICAM-1 and VCAM-1, as well as the number of macrophages around blood vessels, were significantly increased in LOXtg/apoEKO mice compared with control littermates. There were no differences in either the hemodynamic profile or the plasma lipid profile between the 2 groups of animals. LOXtg/apoEKO mice displayed accelerated intramyocardial vasculopathy, and the atheroma-like lesion area was increased 10-fold in the LOXtg/apoEKO mice compared with nontransgenic littermates after 3-weeks on the high-fat diet. Thus, it is demonstrated that LOX-1 overexpression promotes inflammatory intramyocardial vasculopathy in a hyperlipidemic mouse model, and this effect is probably mediated through the endothelial dysfunction induced by overexpression of LOX-1.

Animals↗
PubMed2005

Extracellular HSP70 binding to surface receptors present on antigen presenting cells and endothelial/epithelial cells.

Extracellular HSP70 has been found to participate in both innate and adaptive immune responses. However, little is known about the molecular mechanisms that mediate this process. Previous reports suggest that HSP70 interacts with antigen presenting cells (APC) through a plethora of surface receptors. In this study, we have examined the relative binding of potential HSP70 receptors and found high affinity binding to LOX-1 but not other structures with a role in HSP70-APC interactions such as LRP/CD91, CD40, TLR2, TLR4 or another c-type lectin family member (DC-SIGN) closely related to LOX-1. In addition to APC, HSP70 can avidly bind to non-APC cell lines, especially those from epithelial or endothelial background.

Animals↗
PubMed2005

Angiotensin II increases the expression of lectin-like oxidized low-density lipoprotein receptor-1 in human vascular smooth muscle cells via a lipoxygenase-dependent pathway.

BACKGROUND: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a membrane protein that can act as a surface endocytosis receptor for oxidized LDL (ox-LDL). As increased cellular uptake of ox-LDL by macrophages and activated smooth muscle cells may transform these cells into foam cells, potential interactions among LDL oxidation, ox-LDL uptake, and regulators of vascular smooth muscle cell function are of obvious interest. The objective of this study was to examine the effect of angiotensin II (AII) on the expression of LOX-1 and ox-LDL degradation in human vascular smooth muscle cells (VSMC) METHODS: We performed in vitro experiments in a human VSMC line (T/G HA-VSMC) derived from normal aortic VSMC, using standards methods. RESULTS: We found that AII (10(-7) mol/L) increased the expression of LOX-1 (approximately 2.5-fold, P < .0001) in association with higher degradation of ox-LDL by HA-SMC (from 4019 +/- 529 ng/mg cell protein to 6207 +/- 287 ng/mg cell protein; P = .0033). AII also increased the expression of 12-lipoxygenase (12-LO) and 15-lipoxygenase (15-LO) by approximately 2.2-fold (P = .03) and approximately 3-fold (P = .006), respectively. In addition, AII (10(-7) mol/L) increased the release of 12- and 15-hydroxyeicosatetraenoic acid from VSMC within 10 min approximately 3-fold (P = .03) and 50% (P < .05), respectively. CONCLUSIONS: Our study findings provide evidence that angiotensin II upregulates LOX-1 and 12-LO and 15-LO expression in human VSMC, thereby potentially providing mechanisms for both accelerated LDL oxidation within the cell and the internalization of exogenous ox-LDL, two processes that could increase the susceptibility of human VSMC to further transformation into foam cells.

Angiotensin II↗
PubMed2005

LOX-1 unlocked.

Explore the source record for details and available documents.

Amino Acid Sequence↗
PubMed2005

Essential role of cytoplasmic sequences for cell-surface sorting of the lectin-like oxidized LDL receptor-1 (LOX-1).

Lectin-like oxidized LDL receptor-1 (LOX-1) is an oxidized low-density lipoprotein (OxLDL) receptor found in endothelial cells and a member of the natural killer (NK) receptor gene complex. Here, we demonstrate that the ability of LOX-1 binding to OxLDL distinguishes it from other NK receptors. Domain swapping of the lectin-like domain between LOX-1 and the NK cell receptors CD94, NKG2D, and LY-49A demonstrated the crucial role of this domain for recognition of OxLDL by LOX-1, but not for the correct cell-surface sorting of LOX-1. Using LOX-1 GFP fusion constructs, we find that the combination of cytoplasmic and transmembrane domains of LOX-1 is sufficient to target the chimeric protein to the cell-surface. Using N-terminal deletions we determined that the correct cell-surface localization is dependent on a positively charged motif present in the cytosolic juxtamembrane region of LOX-1. Furthermore, the extracellular localization of the LOX-1 C-terminus is disrupted when we mutated the cytoplasmic basic amino acids, Lys-22, Lys-23 and Lys-25 to Glu. Collectively, these results indicate that the N-terminal cytoplasmic domain of LOX-1 determines the correct expression of the lectin domain on the cell-surface.

Amino Acid Motifs↗
PubMed2005

Nebivolol decreases oxidative stress in essential hypertensive patients and increases nitric oxide by reducing its oxidative inactivation.

OBJECTIVE: To obtain further insight into the mechanism underlying the vasodilator effect of nebivolol. Since oxidative inactivation of nitric oxide (NO) is regarded as an important cause of its decreased biological activity, we studied (1) the effect of nebivolol on some oxidative parameters in essential hypertensive patients; (2) the effect of plasma of nebivolol-treated patients on reactive oxygen species production and NO availability in endothelial cells. METHODS: A total of 20 healthy subjects and 20 matched essential hypertensive patients treated with atenolol or nebivolol according to a double-blind, randomized design participated in the study. We measured low-density lipoprotein (LDL) and plasma hydroperoxides, 8-isoprostanes, oxidized LDL, susceptibility of LDL to oxidation (lag phase) and LDL vitamin E and the effect of plasma of nebivolol- and atenolol-treated patients on reactive oxygen species production and NO availability in endothelial cells exposed to oxidative stress. RESULTS: In hypertensive patients, nebivolol and atenolol significantly reduced blood pressure values after 4 weeks of treatment. Plasma and LDL hydroperoxides, plasma 8-isoprostanes, plasma ox-LDL and LDL lag phase were significantly improved only in the patients receiving nebivolol compared with the atenolol group. Similarly there was a reduction of reactive oxygen species (ROS) and O2*- concentration in endothelial cells exposed to oxidative stress after incubation of the cells with plasma of the patients enrolled in the trial only in the patients receiving nebivolol compared to atenolol group. Furthermore, the reduction of basal and stimulated NO induced by oxidative stress in endothelial cells was significantly lower in the patients receiving nebivolol compared to atenolol group. CONCLUSIONS: The findings of the present study indicate that nebivolol, through its antioxidant properties, increases NO also by decreasing its oxidative inactivation.

Antihypertensive Agents↗
PubMed2005

Different effect of statins on platelet oxidized-LDL receptor (CD36 and LOX-1) expression in hypercholesterolemic subjects.

Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular mortality by decreasing cholesterol as well as by non-lipid-related actions. Oxidized low-density lipoproteins (ox-LDL) are pro-atherogenic molecules and potent platelet agonists. CD36 and lectin-like ox-LDL receptor-1 (LOX-1) are specific ox-LDL receptors also expressed in platelets. This study was planned to address whether treatment with atorvastatin 10 mg/day, pravastatin 40 mg/day or simvastatin 20 mg/day could affect platelet CD36 and LOX-1 expression. Twenty-four patients for each treatment were evaluated after 3, 6, and 9 days and at 6 weeks for complete lipid profile (chromogenic), ox-LDL (ELISA), platelet P-selectin (P-sel), CD36, LOX-1 (FACS), and intracellular citrullin recovery (iCit) (HPLC). Data show hyperactivated platelets (P-sel absolute values, percent variation in activated cells, all p < 0.001), and CD36 and LOX-1 overexpression (all p < 0.001) in patients at baseline. P-sel, CD36, and LOX-1 were significantly decreased by atorvastatin and simvastatin (all p < 0.01) and related with iCit increase (r = 0.58, p < 0.001) and platelet-associated ox-LDL (r = 0.51, p < 0.01) at 9 days. Pravastatin reduced LOX-1 and P-sel (p < 0.05) at 6 weeks in relation with decreased LDL and ox-LDL (r = 0.39, p < 0.01 and r = 0.37, p < 0.01, respectively). These data suggest that atorvastatin and simvastatin reduce platelet activity by exposure of CD36 and LOX-1 before significant LDL reduction, whereas pravastatin action is detected later and in relation with LDL and ox-LDL lowering. Rapid and consistent reduction of CD36 and LOX-1 could be considered a direct anti-atherothrombotic mechanism related to the role of ox-LDL in platelet activation, platelet-endothelium interactions, and NO synthase activity.

Adult↗