Selected CD133⁺ progenitor cells to promote angiogenesis in patients with refractory angina: final results of the PROGENITOR randomized trial.

RATIONALE: Refractory angina constitutes a clinical problem. OBJECTIVE: The aim of this study was to assess the safety and the feasibility of transendocardial injection of CD133(+) cells to foster angiogenesis in patients with refractory angina. METHODS AND RESULTS: In this randomized, double-blinded, multicenter controlled trial, eligible patients were treated with granulocyte colony-stimulating factor, underwent an apheresis and electromechanical mapping, and were randomized to receive treatment with CD133(+) cells or no treatment. The primary end point was the safety of transendocardial injection of CD133(+) cells, as measured by the occurrence of major adverse cardiac and cerebrovascular event at 6 months. Secondary end points analyzed the efficacy. Twenty-eight patients were included (n=19 treatment; n=9 control). At 6 months, 1 patient in each group had ventricular fibrillation and 1 patient in each group died. One patient (treatment group) had a cardiac tamponade during mapping. There were no significant differences between groups with respect to efficacy parameters; however, the comparison within groups showed a significant improvement in the number of angina episodes per month (median absolute difference, -8.5 [95% confidence interval, -15.0 to -4.0]) and in angina functional class in the treatment arm but not in the control group. At 6 months, only 1 simple-photon emission computed tomography (SPECT) parameter: summed score improved significantly in the treatment group at rest and at stress (median absolute difference, -1.0 [95% confidence interval, -1.9 to -0.1]) but not in the control arm. CONCLUSIONS: Our findings support feasibility and safety of transendocardial injection of CD133(+) cells in patients with refractory angina. The promising clinical results and favorable data observed in SPECT summed score may set up the basis to test the efficacy of cell therapy in a larger randomized trial.

Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera.

JAK-STAT signaling through the JAK2V617F mutation is central to the pathogenesis of myeloproliferative neoplasms (MPN). However, other events could precede the JAK2 mutation. The aim of this study is to analyze the phenotypic divergence between polycytemia vera (PV) and essential thrombocytemia (ET) to find novel therapeutics targets by a proteomic and functional approach to identify alternative routes to JAK2 activation. Through 2D-DIGE and mass spectrometry of granulocyte protein from 20 MPN samples, showed differential expression of HSP70 in PV and ET besides other 60 proteins. Immunohistochemistry of 46 MPN bone marrow samples confirmed HSP70 expression. The median of positive granulocytes was 80% in PV (SD 35%) vs. 23% in ET (SD 34.25%). In an ex vivo model KNK437 was used as an inhibition model assay of HSP70, showed dose-dependent inhibition of cell growth and burst formation unit erythroid (BFU-E) in PV and ET, increased apoptosis in the erythroid lineage, and decreased pJAK2 signaling, as well as a specific siRNA for HSP70. These data suggest a key role for HSP70 in proliferation and survival of the erythroid lineage in PV, and may represent a potential therapeutic target in MPN, especially in PV.

Mercury induces proliferation and reduces cell size in vascular smooth muscle cells through MAPK, oxidative stress and cyclooxygenase-2 pathways.

Mercury exposure is known to increase cardiovascular risk but the underlying cellular mechanisms remain undetermined. We analyzed whether chronic exposure to HgCl2 affects vascular structure and the functional properties of vascular smooth muscle cells (VSMC) through oxidative stress/cyclooxygenase-2 dependent pathways. Mesenteric resistance arteries and aortas from Wistar rats treated with HgCl2 (first dose 4.6mgkg(-1), subsequent doses 0.07mgkg(-1)day(-1), 30days) and cultured aortic VSMC stimulated with HgCl2 (0.05-5µg/ml) were used. Treatment of rats with HgCl2 decreased wall thickness of the resistance and conductance vasculature, increased the number of SMC within the media and decreased SMC nucleus size. In VSMCs, exposure to HgCl2: 1) induced a proliferative response and a reduction in cell size; 2) increased superoxide anion production, NADPH oxidase activity, gene and/or protein levels of the NADPH oxidase subunit NOX-1, the EC- and Mn-superoxide dismutases and cyclooxygenase-2 (COX-2); 3) induced activation of ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized the proliferative response and the altered cell size induced by HgCl2. Blockade of ERK1/2 and p38 signaling pathways abolished the HgCl2-induced Nox1 and COX-2 expression and normalized the alterations induced by mercury in cell proliferation and size. In conclusion, long exposure of VSMC to low doses of mercury activates MAPK signaling pathways that result in activation of inflammatory proteins such as NADPH oxidase and COX-2 that in turn induce proliferation of VSMC and changes in cell size. These findings offer further evidence that mercury might be considered an environmental risk factor for cardiovascular disease.

Safety and efficacy of splenectomy in over 65-yrs-old patients with immune thrombocytopenia.

AIM: Few studies specifically focus on elderly splenectomized immune thrombocytopenia (ITP) patients. Older patients with ITP and excellent health are often excluded from surgery splenectomy. We aimed to compare the safety and efficacy of splenectomy in elderly and non-elderly ITP patients and to examine the effect of age on therapeutic response. MATERIAL AND METHODS: We carried out a retrospective analysis of a series of 218 patients who had undergone splenectomy for ITP. We compared the data from the elderly group (≥65 yrs, 57 patients) with the young group (<65 yrs, 162 patients). RESULTS: Surgical technique (laparoscopy or open laparotomy splenectomy) was comparable between the two age groups. The adjusted risk of major bleeding following splenectomy for elderly patients was three times that for young patients (OR 3.05, 95% CI: 1.44-6.52). The median duration of postoperative hospital stay was longer for elderly than for young patients (8 d vs. 4 d, P < 0.001). However, we identified a subgroup of elderly ITP patients, those aged between 65 and 70 yrs who had undergone laparoscopic splenectomy, with a low risk of postoperative complications. Of the 218 patients, 89% achieved a favorable response to splenectomy. A favorable response was significantly less common in elderly than in young people (79% vs. 92%, P = 0.005). However, we observed an acceptable long-term control of ITP in the elderly group, in which the probability of maintaining response for 14 yrs after splenectomy was 56%. CONCLUSIONS: Patients aged ≥65 yrs experienced negative effects on safety and efficacy outcomes of splenectomy for ITP, but further studies are needed to identify predictors of postsplenectomy outcomes in this group.

Relationship between serum levels of triglycerides and vascular inflammation, measured as COX-2, in arteries from diabetic patients: a translational study.

BACKGROUND: Inflammation is a common feature in the majority of cardiovascular disease, including Diabetes Mellitus (DM). Levels of pro-inflammatory markers have been found in increasing levels in serum from diabetic patients (DP). Moreover, levels of Cyclooxygenase-2 (COX-2) are increased in coronary arteries from DP. METHODS: Through a cross-sectional design, patients who underwent CABG were recruited. Vascular smooth muscle cells (VSMC) were cultured and COX-2 was measured by western blot. Biochemical and clinical data were collected from the medical record and by blood testing. COX-2 expression was analyzed in internal mammary artery cross-sections by confocal microscopy. Eventually, PGI2 and PGE2 were assessed from VSMC conditioned media by ELISA. RESULTS: Only a high glucose concentration, but a physiological concentration of triglycerides exposure of cultured human VSMC derived from non-diabetic patients increased COX-2 expression .Diabetic patients showed increasing serum levels of glucose, Hb1ac and triglycerides. The bivariate analysis of the variables showed that triglycerides was positively correlated with the expression of COX-2 in internal mammary arteries from patients (r(2) = 0.214, P < 0.04). CONCLUSIONS: We conclude that is not the glucose blood levels but the triglycerides levels what increases the expression of COX-2 in arteries from DP.

Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL: phase 1b PORTIA study results.

Tisagenlecleucel demonstrated high response rates and a manageable safety profile in adults with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) in the JULIET trial. However, lack of response and chimeric antigen receptor (CAR) T-cell exhaustion were observed in patients with programmed cell death protein 1 (PD-1) overexpression. Hence, pembrolizumab, a PD-1 inhibitor, was hypothesized to improve efficacy and cellular expansion of CAR T-cells in vivo. Here, we report the final analysis of the PORTIA trial in adult patients with r/r DLBCL who had ≥2 prior lines of therapy and had an Eastern Cooperative Oncology Group performance status of ≤1. Patients received 1 tisagenlecleucel infusion on day 1. Pembrolizumab (200 mg) was given every 21 days, for up to 6 doses. Three cohorts initiated pembrolizumab on days 15 (n = 4), 8 (n = 4), or -1 (n = 4). Safety, efficacy, cellular kinetics, and biomarker analyses were included. Tisagenlecleucel plus pembrolizumab was feasible and showed a manageable safety profile, without dose-limiting toxicities. Emerging efficacy with tisagenlecleucel was observed when pembrolizumab was given the day before tisagenlecleucel; however, the limited patient sample and short follow-up do not allow for definitive conclusions. Adding pembrolizumab to tisagenlecleucel did not augment the cellular expansion of tisagenlecleucel but delayed peak expansion if given the day before tisagenlecleucel (NCT03630159).

Identifying Patients with Polycythemia Vera at Risk of Thrombosis after Hydroxyurea Initiation: The Polycythemia Vera-Advanced Integrated Models (PV-AIM) Project.

Patients with polycythemia vera (PV) are at significant risk of thromboembolic events (TE). The PV-AIM study used the Optum® de-identified Electronic Health Record dataset and machine learning to identify markers of TE in a real-world population. Data for 82,960 patients with PV were extracted: 3852 patients were treated with hydroxyurea (HU) only, while 130 patients were treated with HU and then changed to ruxolitinib (HU-ruxolitinib). For HU-alone patients, the annualized incidence rates (IR; per 100 patients) decreased from 8.7 (before HU) to 5.6 (during HU) but increased markedly to 10.5 (continuing HU). Whereas for HU-ruxolitinib patients, the IR decreased from 10.8 (before HU) to 8.4 (during HU) and was maintained at 8.3 (after switching to ruxolitinib). To better understand markers associated with TE risk, we built a machine-learning model for HU-alone patients and validated it using an independent dataset. The model identified lymphocyte percentage (LYP), neutrophil percentage (NEP), and red cell distribution width (RDW) as key markers of TE risk, and optimal thresholds for these markers were established, from which a decision tree was derived. Using these widely used laboratory markers, the decision tree could be used to identify patients at high risk for TE, facilitate treatment decisions, and optimize patient management.

Treatment and Therapeutic Change of Individuals Imprisoned for Child Abuse in the Barcelona Study on Sex Offenders.

The sexual abuse of children is a serious social problem that must be prevented through distinct measures. Among them is the application of treatments to those who have already committed sex crimes in order to prevent them from committing a new one. To assess the efficacy of sexual offense treatment, the most common method has been to compare the recidivism rates of treated and untreated groups. Several meta-analyses in this regard-as well as some specific studies in Spain-have shown that the application of treatment is associated with lower recidivism rates. However, the analysis of the subjects' recidivism alone does not reveal the therapeutic changes that the treatment may elicit in them. Some international studies have evaluated the therapeutic improvements resulting from the application of treatments to men who had sexually abused children. In this context, this study explores the therapeutic changes experienced by a sample of subjects imprisoned for child abuse (N = 145), after participating in the treatment program applied in the Spanish prison system. Nine therapeutic variables were assessed (such as anxiety, cognitive distortions, impulsivity, and social self-esteem), before and after treatment, using an instrument named the Psychological Assessment Scale for Sex Offenders (PASSO). The obtained results show that most of the assessed therapeutic variables improved after treatment, with strong correlations between them. The implications of the results for treatment practice are discussed, as well as the main methodological limitations of this research.

Emerging therapeutic strategies to enhance HDL function.

Epidemiologic studies indicate a strong inverse correlation between plasma levels of high-density lipoproteins (HDL) and cardiovascular disease (CVD). The most relevant cardioprotective mechanism mediated by HDL is thought to be reverse cholesterol transport (RCT). New insights in HDL biology and RCT have allowed the development of promising agents aimed to increase HDL function and promote atherosclerosis regression. In this regard, apo-AI analogs and CETP inhibitors dalcetrapib and anacetrapib have aroused a great interest and opened new expectations in the treatment of CVD.

Conjugation Inhibitors Effectively Prevent Plasmid Transmission in Natural Environments.

Plasmid conjugation is a major route for the spread of antibiotic resistance genes. Inhibiting conjugation has been proposed as a feasible strategy to stop or delay the propagation of antibiotic resistance genes. Several compounds have been shown to be conjugation inhibitors in vitro, specifically targeting the plasmid horizontal transfer machinery. However, the in vivo efficiency and the applicability of these compounds to clinical and environmental settings remained untested. Here we show that the synthetic fatty acid 2-hexadecynoic acid (2-HDA), when used as a fish food supplement, lowers the conjugation frequency of model plasmids up to 10-fold in controlled water microcosms. When added to the food for mice, 2-HDA diminished the conjugation efficiency 50-fold in controlled plasmid transfer assays carried out in the mouse gut. These results demonstrate the in vivo efficiency of conjugation inhibitors, paving the way for their potential application in clinical and environmental settings. IMPORTANCE The spread of antibiotic resistance is considered one of the major threats for global health in the immediate future. A key reason for the speed at which antibiotic resistance spread is the ability of bacteria to share genes with each other. Antibiotic resistance genes harbored in plasmids can be easily transferred to commensal and pathogenic bacteria through a process known as bacterial conjugation. Blocking conjugation is thus a potentially useful strategy to curtail the propagation of antibiotic resistance. Conjugation inhibitors (COINS) are a series of compounds that block conjugation in vitro. Here we show that COINS efficiently block plasmid transmission in two controlled natural environments, water microcosms and the mouse gut. These observations indicate that COIN therapy can be used to prevent the spread of antibiotic resistance.

TGF-beta1: a novel target for cardiovascular pharmacology.

Transforming growth factor beta-1 (TGF-beta1) plays a key role in cardiovascular disease by a process which allows the loss of its protective properties. The first therapeutic attempt to restore its function by selectively designed novel drugs are being made. In addition, it has been recognized that the TGF-beta1 pathway is involved in the vascular mechanism of action of some current clinical drugs, such as acetylsalicylic acid, thiazolidinediones and statins. The aim of this paper is to review the possible value of TGF-beta1 as both a disease marker and a therapeutical target for cardiovascular disease.

High-reproducible flow cytometric endothelial progenitor cell determination in human peripheral blood as CD34+/CD144+/CD3- lymphocyte sub-population.

Although determination of circulating endothelial progenitor cell (EPC) in peripheral blood by flow cytometry is an emerging marker for cardiovascular medicine, a common standardized protocol is still not available, due to the low numbers achieved in peripheral blood. In the present paper we describe a novel technique for EPC quantification as CD34+/CD144+/CD3- cells within the lymphocyte gate, which increases the percentages of EPC positivity described before and also offers high intra-assay reproducibility. These improvements are based on a gating strategy for big-sized lymphocytes, smooth fixation and cytometric clearance of CD3+ lymphocytes (T-cells). This last procedure is able to increase intra-assay Pearson's correlation from 0.8517 to 0.8908. Therefore, the technical setting described here offers a high-performance and clinically oriented EPC determination strategy in human peripheral blood.

Human vascular smooth muscle cells from diabetic patients are resistant to induced apoptosis due to high Bcl-2 expression.

An emerging body of evidence suggests that vascular remodeling in diabetic patients involves a perturbation of the balance between cell proliferation and cell death. Our aim was to study whether arteries and vascular smooth muscle cells (VSMCs) isolated from diabetic patients exhibit resistance to apoptosis induced by several stimuli. Internal mammary arteries (IMAs) were obtained from patients who had undergone coronary artery bypass graft surgery. Arteries from diabetic patients showed increasing levels of Bcl-2 expression in the media layer, measured by immunofluorescence and by Western blotting. Human IMA VSMCs from diabetic patients showed resistance to apoptosis, measured as DNA fragmentation and caspase-3 activation, induced by C-reactive protein (CRP) and other stimuli, such as hydrogen peroxide and 7beta-hydroxycholesterol. The diabetic cells also exhibited overexpression of Bcl-2. Knockdown of Bcl-2 expression with Bcl-2 siRNA in cells from diabetic patients reversed the resistance to induced apoptosis. Consistent with the above, we found that pretreatment of nondiabetic VSMCs with high glucose abolished the degradation of Bcl-2 induced by CRP. Moreover, cell proliferation was increased in diabetic compared with nondiabetic cells. This differential effect was potentiated by glucose. We conclude that the data provide strong evidence that arterial remodeling in diabetic patients results from a combination of decreased apoptosis and increased proliferation.

Biphasic effect of pioglitazone on isolated human endothelial progenitor cells: involvement of peroxisome proliferator-activated receptor-gamma and transforming growth factor-beta1.

Endothelial progenitor cells (EPCs) have been implicated in vascular repair and found to be functionally impaired in patients with diabetes. We evaluated the effects of the anti-diabetic drug pioglitazone on human EPC function and the involvement of PPAR-gamma and TGF-beta1. EPCs in culture were characterized at day 7 by the development of colony-forming units (CFUs) and flow cytometry assessment of differentiation marker (DiI-ac-LDL/lectin, KDR and CD31). Adhesion on fibronectin and fibrinogen in flow was analyzed as functional parameter. Treatment with pioglitazone for 72 hours increased the number of EPC-CFUs, DiI-ac-LDL(+)/lectin(+), CD31(+) and KDR(+) EPCs at 1 microM but not at 10 microM. Since pioglitazone did not significantly alter proliferation and apoptosis in cultured EPCs, the increase in EPC number was most likely attributable to augmented adhesion and differentiation. Indeed, pioglitazone increased EPC adhesion in flow at 1 microM, an effect prevented by PPAR-gamma and beta2-integrin blockade. In contrast, pioglitazone did not promote EPC adhesion at 10 microM; however, increased adhesion became evident by co-incubation with a blocking TGF-beta1 antibody. As determined by ELISA, pioglitazone induced a persistent increase in TGF-beta1 secretion only at 10 microM when a significantly elevated expression of endoglin, the accessory receptor for TGF-beta1, was also observed. Taken together, pioglitazone exerts biphasic effects on the function of isolated EPCs, causing a PPAR-gamma-dependent stimulation at 1 microM and a TGF-beta1-mediated suppression at 10 microM. These results may help to define optimal therapeutic doses of pioglitazone for improving endothelial dysfunction.

Role of TGF-beta1 in vascular smooth muscle cell apoptosis induced by angiotensin II.

Both Angiotensin II and transforming growth factor beta-1 (TGF-beta1) are important mediators of vascular smooth muscle cell function and have been reported to mediate the balance between proliferation and apoptosis. Some crosstalk between Angiotensin II and TGF-beta1 in end-organ hypertension has been established. However, whether TGF-beta1 is able to mediate Angiotensin II-induced vascular cell damage remains unknown. Vascular smooth muscle cells were obtained from rat thoracic aorta and cultured in 10% foetal calf serum. In all experiments, medium was changed to a low-serum (0.4% foetal calf serum) or serum-free one with or without Angiotensin II. Apoptosis was assessed by DNA fragmentation, DNA synthesis was measured as bromo-deoxyuridine uptake. TGF-beta1 production was determined by Enzyme-linked Immunosorbent Assay (ELISA) from cell conditioned media, RT-PCR from cell lysates and confocal immunostaining of fixed cells. Angiotensin II induced apoptosis in the absence of DNA synthesis when coincubated at 1 microM. Neither the specific anti-TGF-beta1 monoclonal antibody (50 microg/ml) nor the novel activin-like kinase (ALK)-4/5/7 synthetic inhibitor SB-431542 (4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide) at 10 microM were able to inhibit this effect. Angiotensin II induced expression of TGF-beta1 without further secretion of this cytokine. This effect was not affected by incubation with the AT1 inhibitor irbesartan (10 microM). A pharmacological approach to TGF-beta1 inhibition would be unable to reverse the apoptotic effect of Angiotensin II on vascular smooth muscle cells.

Importance of intracellular angiotensin II in vascular smooth muscle cell apoptosis: inhibition by the angiotensin AT1 receptor antagonist irbesartan.

The intracellular uptake of Angiotensin II has been described, although its physiological role is not yet understood. We aimed to study the role of Angiotensin II internalization in Angiotensin II-induced apoptosis. Vascular smooth muscle cells were cultured from male Wistar-Kyoto rats and treated with Angiotensin II (1 microM, 48 h). Apoptosis was assessed by DNA fragmentation, cell cytometry and caspase-3 activity. The Angiotensin AT(1) receptor antagonist irbesartan (0.1-10 microM) and the inhibitors of Angiotensin II internalization phenylarsine oxide (PAO, 20 microM), but not the AT(2) receptor antagonist PD123319 (S-(+)-1-[(4-(Dimethylamino)-3-methylphenyl)methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid di(trifluoroacetate) salt), decreased Angiotensin II-mediated apoptosis. Pre-treatment with irbesartan, but not with PD123319, blocked Angiotensin II internalization. We found a strong correlation between intracellular Angiotensin II staining and Angiotensin II-induced apoptosis for all compared groups. We therefore conclude that internalization of Angiotensin II is involved in apoptosis of vascular smooth muscle cells induced by this peptide.

A Dynamic Risk Factors-Based Typology of Sexual Offenders.

The purpose of this article was to develop an Spanish psychometric typology of sexual offenders taking into account dynamic risk factors. The sample comprised 94 sex offenders imprisoned in Spain (52 rapists and 42 child molesters). The analysis yielded two different offender categories based on the subjects' criminogenic needs level (high and low). The results also showed that social desirability has a strong influence on the developed typologies, whereas the offence type, sociodemographic characteristics, and criminal history do not. A dynamic risk factors typology, such as the one proposed here, could help criminal and correctional facilities to fulfill their remit. It could also be useful for linking treatment intensity to offenders' criminogenic needs, as well as providing a platform for recidivism risk assessments.

Towards a taxonomy of conjugative plasmids.

Conjugative plasmids are the keystone of horizontal gene transfer. Metagenomic research and clinical understanding of plasmid transmission beg for a taxonomical approach to conjugative plasmid classification. Up to now, a meaningful classification was difficult to achieve for lack of appropriate analytical tools. The advent of the genomic era revolutionized the landscape, offering a plethora of plasmid sequences as well as bioinformatic analytical tools. Given the need and the opportunity, in view of the available evidence, a taxonomy of conjugative plasmids is proposed in the hope that it will leverage plasmid studies.

Pioglitazone induces vascular smooth muscle cell apoptosis through a peroxisome proliferator-activated receptor-gamma, transforming growth factor-beta1, and a Smad2-dependent mechanism.

Thiazolidinediones, such as pioglitazone, seem to exert direct antiatherosclerotic and antirestenotic effects on type 2 diabetes, in part due to an induction of vascular smooth muscle cell (VSMC) apoptosis. We aimed to study the role of transforming growth factor (TGF)-beta in rat aortic VSMC. Pioglitazone at 100 micromol/l increased apoptosis without affecting DNA synthesis, and this effect was reversed by an anti-TGF-beta1 antibody. Extracellular TGF-beta1 levels were rapidly increased after treatment with pioglitazone in a peroxisome proliferator-activated receptor (PPAR)-gamma-dependent mechanism because this secretion was blocked by the PPAR-gamma inhibitor GW9662. Pioglitazone subsequently increased the nuclear recruitment of phospho-Smad2, without any effect on protein expression. According to our results, we propose that the apoptotic effect of pioglitazone on VSMC depends on the following sequence: PPAR-gamma activation, TGF-beta1 release, and selective phospho-Smad2 nuclear recruitment. Management of Smad signaling on VSMC might provide future clinical benefits in vascular diseases.

Kaempferol inhibits apoptosis in vascular smooth muscle induced by a component of oxidized LDL.

Antioxidants such as flavonoids afford protection against oxysterols-induced toxicity. We have investigated the effect of kaempferol and rutin, active components of red wine, in the apoptosis induced by 7beta-hydroxycholesterol in rat vascular smooth muscle cells. 7beta-Hydroxycholesterol induced apoptosis in vascular smooth muscle which include BcL-x(L) degradation, caspase-3 activation and DNA fragmentation. The apoptosis induced by 7beta-hydroxycholesterol was prevented by pretreatment with kaempferol (10-30 microM), but not with rutin. Interestingly preincubation with the estrogen receptor alpha antagonist ICI 182,780 (1 microM) prior to kaempferol partially reverted the antiapoptotic effect of this flavonoid on caspase-3 activation and DNA fragmentation induced by 7beta-hydroxycholesterol. In conclusion, the flavonoid kaempferol, unlike rutin, diminished the apoptosis induced by a component of oxidized low-density lipproteins (oxLDL). This effect was partially mediated by the estrogen receptor alpha.