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Chronic underlying inflammation is involved in the pathophysiology of coronary artery disease (CAD). Polyalthia longifolia var. pendula bark extract (PLE) is known to exhibit anti-inflammatory activity and has high content of phytosteroids. Since phytosteroids mimic estrogen structurally, we postulated that PLE may provide protection in postmenopausal women against CAD. Thus the effect of PLE has been explored on expression of estrogen receptors (ERalpha and ERbeta) and inflammatory inducible nitric oxide synthase (iNOS) genes in vitro in peripheral blood mononuclear cells (PBMCs) obtained from postmenopausal women. A total of 20 postmenopausal women were included in the present study. Group I (N = 10) included women with angiographically proven CAD, and group II (N = 10) is composed of equal number of age-matched healthy postmenopausal females as controls. Significantly low levels of serum 17-beta estradiol were observed in subjects of group I as compared to group II (p0.01). A marked increase in L: -citrulline levels (p0.05) and significantly augmented levels of reactive nitrogen intermediates (p0.05) were observed in group I subjects. PLE significantly attenuated PMA-induced expression of both ERalpha and ERbeta receptors and inflammatory iNOS gene in vitro in a dose- and time-dependent manner and had an additive effect on these genes when compared with tamoxifen. Ours is the first report to demonstrate that PLE contains certain bioactive principles, which possess anti-inflammatory and estrogenic properties, and thereby hold the promise to be screened for their anti-atherogenic potential in experimental animals to favorably alter several other markers of cardiovascular risk.

Inflammation participates in atherosclerosis from its inception onwards. RAGE (receptor for advanced glycation end products) and its natural pro-inflammatory ligand, EN-RAGE (extracellular newly identified RAGE-binding protein) have been implicated in various inflammatory diseases. In present study, we determined the expression of RAGE and EN-RAGE in peripheral blood mononuclear cells (PBMCs) of subjects with pre-mature coronary artery disease (CAD) for the first time.The study patients were angiographically proven non-diabetic patients with pre-mature CAD (Group I; N=100) and control group comprised of subjects with coronary risk factors and without coronary artery lesions (Group II; N=40). Semi-quantitative RT-PCR was performed to determine transcriptional expression of RAGE and EN-RAGE in PBMCs. Soluble RAGE (sRAGE) and C-reactive protein (hsCRP) levels were determined in serum of all study subjects using immunoassays. A significantly increased transcriptional expression of RAGE and EN-RAGE in PBMCs (p0.01) of Group I patients was observed. Increased circulating hsCRP (p0.01) levels and decreased sRAGE (p0.01) levels were observed in Group I as compared with the Group II subjects. Severity of disease determined by Gensini score was found to be positively correlated with transcriptional expression of RAGE (r=0.530) and EN-RAGE (r=0.323). EN-RAGE expression revealed a strong association with RAGE (r=0.326), hsCRP (r=0.251) and a negative association with sRAGE (r=-0.222).Increased expression of RAGE and EN-RAGE in non-diabetic pre-mature CAD and various associations discussed may amplify several cellular perturbations and thus significantly contribute to the pathophysiology of CAD.

Background Left main disease (LMD), defined as ≥ 50% lesion stenosis, occurs in 3% to 5% of patients undergoing catheterization. Limited data on the value of single-photon emission computed tomography (SPECT) imaging for diagnosis of LMD exists. Hypothesis This study sought to evaluate the diagnostic accuracy of SPECT imaging in the diagnosis of LMD. Methods A total of 74 consecutive patients with LMD, identified from our catheterization lab database (January 2003–December 2007) with gated exercise (15 patients) or adenosine (59 patients), thallium 201, or Tc-99m SPECT imaging within 6 months of index angiography were included. Group 1 (Gp 1) included 33 patients with isolated LMD. Group 2 (Gp 2) consisted of 41 patients with LMD and 1-vessel disease (6); LMD and 2-vessel disease (24); and LMD and 3-vessel disease (11). Results Reversible perfusion defects (PD) were absent in 6 (18%) of Gp 1 and 8 (20%) of Gp 2 patients. Among Gp 1 patients, PD in 1-vessel, 2-vessel, 3-vessel distribution were seen in 20 (61%), 5 (15%), and 2 (6%) patients respectively. In comparison, PD in 1-vessel, 2-vessel, 3-vessel distribution were observed in 20 (49%), 12 (29%), and 1 (2%) of Gp 2 patients respectively. Left main (LM) pattern was noted in 6 patients (Gp 1: 2, Gp 2: 4). Transient ischemic dilatation (TID) was encountered in 34 patients (Gp 1: 17, Gp 2: 17) and in 4 patients with normal perfusion scans. Conclusions These data represent the largest analysis of patients with “isolated” LMD. Approximately 19% of patients with LMD have no reversible PD on SPECT. While LM pattern is rare, 1-vessel distribution PD and TID represent the most frequent SPECT abnormalities. Copyright © 2009 Wiley Periodicals, Inc.

Aortic valve calcification is common in the elderly and in patients with congenital bicuspid aortic valve but unlike calcific mitral valve disease it is not a well recognized risk factor for stroke. Although autopsy studies have revealed evidence of systemic embolism in one-third of cases with calcific aortic valves, there is conflicting data from larger clinical studies examining the association between calcific aortic valve and stroke. There are only 8 reported cases of symptomatic stroke from spontaneous cerebral thromboembolism associated with calcific aortic valve in the literature. Computerized tomography (CT) angiography and CT without contrast are modalities of choice to diagnose calcific embolism, while MRI may be useful in delineating the extent of ischemia. Ideal management strategy, the role of antiplatelet therapy, anticoagulation or recommendations for valve replacements are poorly defined. We present a focused literature review on this topic.

Background: Acute coronary syndrome (ACS) resulting from culprit lesion in left main coronary artery (LMCA) can cause rapid hemodynamic deterioration. It is important to identify these patients early to facilitate timely revascularization. ST segment elevation in aVR greater than or equal to V 1 (aVR-V 1 ≥ 0) has been suggested as a sensitive predictor of LMCA disease. As a result of balanced forces, we hypothesized that ST deviation in V 6 greater than or equal to ST deviation in V 1 (V 6 -V 1 ≥ 0) might be a good determinant of LMCA disease. Methods: We compared admission 12-lead ECGs of ACS resulting from culprit LMCA lesion (n = 75, group I) with ACS resulting from culprit left anterior descending lesion (n = 81, group II). Group I was selected over a period of 10 years. We compared V 6 -V 1 ≥ 0 to aVR-V 1 ≥ 0 in both groups. We also looked at ratios of ST deviations in V 6 ,V 1 (V 6 /V 1 ≥ 1) and aVR,V 1 (aVR/V 1 ≥ 1) in patients where ST segment in V 1 was not isoelectric (group I = 54 and group II = 55). Results: ST deviation in V 6 was significantly greater in group I as compared to group II (P < 0.001). The reliabilities of V 6 -V 1 ≥ 0, V 6 /V 1 ≥ 1, aVR-V 1 ≥ 0, and aVR/V 1 ≥ 1 in predicting LMCA disease were determined. Conclusion: This is the largest series of ECG analysis on ACS resulting from culprit LMCA lesion. V 6 -V 1 ≥ 0 and V 6 /V 1 ≥ 1 were more sensitive in predicting LMCA as culprit vessel in comparison to previously reported greater ST segment elevation in aVR than V 1 .

Purpose Normal tissue toxicity remains a dose limitation for cancer radiotherapy and chemoradiotherapy. Growth factors offer a novel means of mitigating normal tissue radiotoxicity. In particular, keratinocyte growth factor (rHuKGF), whose proliferative activity is restricted to epithelial cells, holds promise on the basis of the findings of preclinical models of epithelial cytoprotection and the clinical developments to date. We report the radioprotection of murine lung by an increase in tissue cellularity after rHuKGF-induced proliferation. Methods and materials Flow cytometric and image analysis techniques after bromodeoxyuridine labeling were used to estimate proliferative parameters. Our specialized analytical methods measure not only labeling indexes, but also the durations of S and G 2 +M phases, potential doubling times, and the net cell production rate. Image analysis techniques were used to identify the specific cell types that were proliferating (type II pneumocytes). Results Lung labeling index control values (0.5%) rose to a maximum (5.5%) at 3 days after intratracheal rHuKGF, returning to normal by Day 7. The potential doubling time fell from 66 days to 4.4 days. The net cell production rate rose from a control value of 1%/d to >15%/d by Day 3. This resulted in a nearly twofold increase in alveolar epithelial cellularity, which remained significantly elevated on Day 7. Saline-treated control animals exhibited no significant changes in the proliferative parameter values or cellularity. On the basis of these data, mice were irradiated, solely to the thorax, with ranges of single doses of 250 kVp X-rays 7 days after either intratracheal administration of 5 mg/kg rHuKGF or phospate-buffered saline. This interval was chosen because the proliferative response of the type II cells was finished but the cellularity of the lung remained increased. Pretreatment with rHuKGF extended the latent period before onset of pneumonitis after all radiation doses. rHuKGF treatment 7 days before thoracic irradiation significantly protected against pneumonitis (median effective dose 13.7 Gy, 95% confidence limit 13.4–14.0) compared with the control pretreatment with phosphate-buffered saline (median effective dose 12.8 Gy, 95% confidence limit 12.6–13.1). Conclusion The data showed that an increase in tissue cellularity, caused by rHuKGF treatment before irradiation, protected the lung from damage due to pneumonitis.

The goal of this study was to assess the clinical applicability of molecular genetic techniques in the study of minimal residual disease (MRD) in pediatric acute myeloid leukemia (AML) via DNA and RNA-based methods. Currently, multi-parametric flow cytometry (MPFC) for surface immunophenotypes is the gold standard for MRD with a limit of detection between 0.001-0.002. However, approximately one-third of children with no detectable MRD by MPFC after first induction still relapse and suffer inferior outcomes. One potential reason is that a majority of refractory or recurrent AML clones will present with altered immunophenotypes compared to diagnostic specimens. In contrast, DNA mutations present at diagnosis will remain in refractory disease and therefore, a gene-based MRD platform surveying many genes could enable targeted, gene-specific therapy. Recently, the heterogeneous and unique genomic landscape of pediatric AML was characterized in the TARGET project and highlights the potential for leveraging companion molecular screens in the analysis of AML MRD. Contrary to adult AML, pediatric AML is not primarily characterized by single nucleotide variants (SNVs), but rather by complex structural variants (SV) that are difficult to detect using standard next generation sequencing techniques and analysis pipelines. The need to detect these complex SV and SNVs, all of which are at low allelic ratios (AR) at the remission state, demands assays that are capable of analyzing both DNA and RNA molecules at levels of detection comparable to MPFC. As proof of principal, we leveraged a unique capture technique (ArcherDx; CoreAML) to detect an important SV in pediatric AML, the internal tandem duplication in Fms related tyrosine Kinase (FLT3-ITD). Via a serial dilution of cells with known FLT3-ITD allelic ratio (MV4-11 cells), to determine a limit of detection, we were able to detect the mutation as low as 0.001. Next, we bench-marked the technique using diagnostic and relapse samples, and successfully detected FLT3-ITD at AR To complement the DNA-based approach, we compared two error-corrected (EC) RNA assays (a Druley lab developed protocol and the ArcherDx; HemeV2 panel) to further assay SVs that cause novel gene fusions and aberrant exon usage, which are not detectable via DNA assays. Compared to existing cytogenetic and RNA-seq data, this new platform was capable of detecting known and novel cryptic translocations. Finally, we integrated the results from the FLT3-ITD assay and the RNA assay with our custom error-corrected sequencing data to create a novel bioinformatics workflow for assessing the biological implications of MRD clones detected. Collectively, our data support that EC sequencing, at both the DNA and RNA level, enable accurate detection of low allelic variants that could be used for improved clinical MRD diagnostics, prognostication and therapeutic selection. Citation Format: Erin L. Crowgey, Nitin Mahajan, Wing H. Wong, Edward A. Kolb, Todd Druley. Sensitive and specific DNA and RNA sequencing techniques for detecting minimal residual disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4878. doi:10.1158/1538-7445.AM2017-4878

The retinoblastoma gene (RB1) has been implicated as a tumor suppressor in multiple myeloma (MM), yet its role remains unclear because in the majority of cases with 13q14 deletions, un-mutated RB1 remains expressed from the retained allele. To explore the role of Rb1 in MM, we examined the functional consequences of single- and double-copy Rb1 loss in germinal center B cells, the cells of origin of MM. We generated mice without Rb1 function in germinal center B cells by crossing Rb1(Flox/Flox) with C-γ-1-Cre (Cγ1) mice expressing the Cre recombinase in class-switched B cells in a p107(-/-) background to prevent p107 from compensating for Rb1 loss (Cγ1-Rb1(F/F)-p107(-/-)). All mice developed normally, but B cells with two copies of Rb1 deleted (Cγ1-Rb1(F/F)-p107(-/-)) exhibited increased proliferation and cell death compared with Cγ1-Rb1(+/+)-p107(-/-) controls ex vivo. In vivo, Cγ1-Rb1(F/F)-p107(-/-) mice had a lower percentage of splenic B220+ cells and reduced numbers of bone marrow antigen-specific secreting cells compared with control mice. Our data indicate that Rb1 loss induces both cell proliferation and death in germinal center B cells. Because no B-cell malignancies developed after 1 year of observation, our data also suggest that Rb1 loss is not sufficient to transform post-germinal center B cells and that additional, specific mutations are likely required to cooperate with Rb1 loss to induce malignant transformation.

Takayasu’s arteritis (TA) was reported as an eye disease in the year 1905 and later was confirmed as a vasculitis. Since then, the etiology of the disease remains unknown; however, characteristic clinical features suggest multiple causative factors. Recent progress in vascular biology and other disciplines enlightens the pathophysiology of TA and demonstrated induction of various nonspecific inflammatory symptoms and destruction of the arterial wall, which leads to aneurysms and rupture of the affected arteries. Matrix metalloproteinases (MMPs) as an enzyme family have well-established roles in several vascular pathologies including intima formation, atherosclerosiss and aneurysms. MMPs have been proposed to be one of the molecules with a potential of having dual role in the course of TA, first as an active participant in pathophysiology and secondly as a diagnostic biomarker for TA disease. The desire to improve our understanding of the importance of MMPs and their endogenous inhibitors (TIMPs) in TA disease and for the development of therapeutic agents has inspired basic and clinical scientists for over a decade. In the present paper, we summarized the scientific rationale which highlights the signatures of matrix metalloproteinases and their endogenous inhibitors in pathophysiology as well as their being a potential candidate as biomarker for Takayasu’s arteritis.

Systolic blood pressure (SBP) rises approximately linearly with age in most societies. The cause of this rise is unclear. We tested the hypothesis that SBP is causally associated with the rate of rise in SBP with age by evaluating the effect of 12 polymorphisms associated with lower SBP on the age-related rate of rise in SBP in a series of meta-regression analyses involving ≤199 477 participants in 63 studies. We then evaluated the effect of these polymorphisms on the odds of coronary heart disease in 22 223 case and 64 762 control subjects and compared it with the effect of lower SBP observed in both prospective cohort studies and blood pressure–lowering randomized trials. All 12 polymorphisms were associated with both lower SBP and a slower age-related rise in SBP. The weighted mean effect of these 12 polymorphisms was associated with a 0.32-mm Hg lower SBP ( P =1.79×10 −7 ) and a 0.093-mm Hg/decade slower age-related rise in SBP ( P =3.05×10 −5 ). The effect of long-term exposure to lower SBP on coronary heart disease mediated by these polymorphisms was 2-fold greater than that observed in prospective cohort studies ( P =0.006) and 3-fold greater than that observed in short-term blood pressure treatment trials ( P =0.001). We conclude therefore that SBP seems to be causally associated with the rate of rise in SBP with age and has a cumulative effect on the risk of coronary heart disease.

Background Oxidative stress and activation of matrix metalloproteinases (MMPs) together have been widely implicated in various inflammatory vascular disorders. As Takayasu's arteritis (TA) is an inflammatory disorder characterized by destruction of elastic fibers, we hypothesized that oxidative stress and MMPs might play an important role in pathophysiology of the disease. Methods 40 patients with clinically defined TA and equal number of normal, healthy, controls were enrolled in the study. Subjects with TA were further divided into clinically active disease or in remission phase of the disease. Results Augmented levels of 8-isoPGF 2α (238.9±125.7 vs 79.5±29.1ng/ml), nitrite (NO 2 − ) (14.9±15.6 vs 3.3±1.7μM) were observed in TA patients as compared to the controls ( p 2α (272.2±117.3 vs 105.9±43.5ng/ml) and NO 2 − (17.9±16.1 vs 3.1±2.5μM) levels were higher in subjects with active disease vs those in remission ( p p p >0.05). Further, gelatinolytic activity showed a positive correlation with 8-iso-PGF 2α and NO levels in patients with TA. Conclusions Increased oxidative stress and MMP activity may play an active role in the progression of Takayasu's arteritis disease.

Background Congestive heart failure in sinus rhythm ranks second after atrial fibrillation (AF) among cardiogenic risk-factors for stroke. Clinical and echocardiographic predictors of stroke in this high-risk population remain poorly defined. Methods Retrospective screening of 1886 consecutive patients with severe systolic dysfunction (LVEF ≤35%) at a tertiary medical center echocardiography database (Nov 2005–Sep 2008) identified 83 patients in sinus rhythm with cardioembolic stroke. Patients with AF on follow-up, prosthetic valve, ventricular arrhythmia and lack of consensus between reviewing neurologists were excluded ( n =10). Consecutive age and gender-matched controls in sinus rhythm formed GpII ( n =73). Results The incidence of stroke was 3.9% (73/1886) over 35 months in this study. There were no significant differences in prevalence of established clinical risk-factors for stroke. There was a significantly higher prevalence of LV non-compaction ( p =0.02), aneurysm ( p p p Conclusions LV non-compaction, aneurysm, spontaneous echo-contrast and pulmonary hypertension are associated with an increased risk of stroke. While anticoagulation of these high-risk subgroups appears reasonable, further study in a prospective randomized clinical trial merits consideration.

Hypertension is a disorder controlled by multiple genes and inflammation and vascular remodelling of arteries have been implicated in pathogenesis of this disease. Green tea polyphenols (GrTPs) are rich in antioxidants and are known to inhibit inflammatory responses. A significant time-dependent increase in mRNA expression of both IL-6 and MMP-9 were observed in THP-1 macrophages when cultured in normocholesterolaemic hypertensive sera (P

Objectives: Essential hypertension (EH) is a multifactorial disease and oxidative stress has been demonstrated to play an important role in its pathophysiology. Among several genes implicated in the pathophysiology of hypertension, endothelin-2 (ET-2), a potent vasoconstrictor, has been incriminated as a candidate gene for essential hypertension. To find out correlation of in vivo biomarkers of oxidative stress [oxidized low density lipoprotein (Ox-LDL), 8-iso- Prostaglandin F2α (8-iso-PGF2α)] and Nitrite (NO2-) are related to endothelin-2 levels and to determine their value as diagnostic markers in essential hypertension. Methods: 100 subjects with essential hypertension and 150 age and sex-matched normotensive controls were enrolled to determine levels of ET-2, Ox-LDL, 8-iso-PGF2α and NO2-. Results: We observed significantly augmented levels of ET-2 (P

The importance of epigenetic alterations such as DNA methylation, histone modification and nucleosome remodeling in breast cancer is well established. Epigenetic alterations are reversible, and much research has been focused on understanding these alterations with the aim of developing effective therapies. Prostate-derived Ets factor (PDEF) is a member of the Ets family of transcription factors and has long been under investigation for its key role in tumor development and progression. To date, no studies have been conducted to elucidate the epigenetic modifications of PDEF in cancer progression. Using breast and prostate cancer cells, we investigated the effect of the methylation inhibitor 5' azacytidine (AZA) on the expression of PDEF in these cells. The inhibition of methylation observed was specific to breast cancer cells as experiments with prostate cells did not exhibit any significant change. Notably, the expression of p21, a cyclin-dependent kinase (CDK) inhibitor 1 and also a target gene of PDEF, was found to be positively correlated with PDEF expression following 5'AZA treatment. Inhibition of methylation led to a decrease in the proliferation rate of MDA-MB-468 cells as revealed by MTT proliferation assay. Other epigenetic alterations such as histone modifications were not observed in these breast cancer cells following treatment with specific HDAC inhibitors. Our data suggest the possibility of epigenetic modification of PDEF due to DNA methylation and involvement of the cell cycle inhibitor p21. Future studies on the epigenetic alterations of PDEF in correlation with p21 or other targets may facilitate the development of effective therapies for the treatment of breast cancer.

Maspin is a member of the serine protease inhibitor (serpin) superfamily and displays tumor-suppressing activity by controlling cell migration, proliferation, apoptosis, and adhesion. Here, we provide evidence that maspin acts as a reactive oxygen species (ROS) scavenger through oxidation of three structurally exposed cysteine thiols to sulfenic acid. Ablation of these cysteine residues in maspin resulted in a significant increase in total ROS production in mouse mammary TM40D cells. Also, cells containing a triple-cysteine mutant of maspin showed elevated ERK1/2 activity, a downstream target of ROS, and enhanced proliferation and colony formation. These findings establish a novel mechanism by which maspin utilizes its cysteine thiols to inhibit oxidative stress and cell growth.

Historically, the receptor for advanced glycation end products (RAGE) was thought to exclusively play an important role under hyperglycemic conditions. However, more and more evidence suggests that RAGE in fact is an inflammation perpetuating multi-ligand receptor and participates actively in various vascular and inflammatory diseases even in normoglycaemic conditions. Various ligands include advanced glycation end products (AGEs), S100 proteins and amphoterins etc. Besides full-length RAGE, numerous truncated forms of the receptor have also been described including the well-characterized soluble RAGE (sRAGE). sRAGE has an ability to act as a decoy to avoid interaction of RAGE with its pro-inflammatory ligands. Ligand engagement of RAGE activates multiple signaling pathways and also forms a positive feedback loop for its own enhanced expression. This review will discuss the role of multi-ligand receptor i.e. RAGE in context to various vascular diseases, which have a pathophysiologically important inflammatory component in normoglycaemic conditions.

Coronary atherosclerosis is a chronic progressive disease that begins early in life and progresses slowly over several decades before becoming clinically manifest. The causal relationship between low-density lipoprotein cholesterol (LDL-C) and the risk of coronary atherosclerosis is well established. Multiple randomized trials have demonstrated that lowering LDL-C levels during treatment with a statin reduces the risk of major atherosclerotic coronary events. However, individuals being treated with a statin continue to experience a high residual risk of events. Here we review the evidence that lowering LDL-C levels beginning earlier in life, and therefore earlier in the atherosclerotic disease process, can prevent or substantially delay the development of atherosclerosis and thereby substantially improve the clinical benefit of therapies that lower LDL-C levels. We focus on providing a critical appraisal of the naturally randomized evidence that is emerging from recently conducted genetic association studies.

Takayasu's arteritis (TA) is a rare primary and granulomatous large vessel vasculitis of unknown origin that predominantly affects the aorta and itsmajor branches. It has been shown toaffect individuals of anyage, gender and a wide variety of ethnic and racial population worldwide. The pathophysiology of TA is complex and multi-factorial and the exact pathogenesis remains to be elucidated; however, participation of autoimmunity, inflammation and oxidative stress has potentially been implicated [1–3]. Receptor for advanced glycation endproducts (RAGE) is amemberof the immunoglobulin superfamily and is expressed on the surface of various cells e.g. endothelium, mononuclear phagocytes, lymphocytes and smooth muscle cells. Extracellular newly identified RAGE-binding protein (EN-RAGE or S100A12), an inflammatory ligand of RAGE, is a member of the S100 protein family. Since its discovery twodecades back [4], the inflammatory role of RAGE and EN-RAGE interaction is nowwell established in various chronic inflammatory disorders. RAGE has a circulating truncated variant isoform and soluble RAGE (sRAGE), corresponds to its extracellular domain only. By competing with cell-surface RAGE for ligand binding, sRAGE contributes to the removal/neutralization of circulating ligands, thus, functioning as a decoy [5–7]. Previously, we demonstrated low sRAGE levels showing inverse correlation with MMPs in a group of forty TA subjects as compared to controls [8]. Keeping in mind the importance of RAGE biology in various diseases, we thought it worth to determine the expression of RAGE and its inflammatory ligand EN-RAGE at transcriptional level in peripheral blood mononuclear cells (PBMCs) fromTA subjects. For this, 24 subjectswith TA and 24 normal healthy controls were recruited as described previously [3,8,9]. The Institutional Ethics Committee approved the present study. Venous blood was collected from overnight fasted individuals in the morning from antecubital vein and processed as described previously [5,8]. Semi-quantitative RT-PCR was performed for determining the transcriptional expression of RAGE andEN-RAGE in PBMCs [5]. Circulating levels of sRAGE were determined in all the study subjects using commercially available enzyme-linked immunoassay as per manufacturer's instructions (DRG00, RD p=0.003, Fig. 1E). However, no significant correlation of sRAGE levels was observed with either RAGE or EN-RAGE mRNA in TA subjects. This is the first report in literature which demonstrates that mRNA levels of RAGE and its ligand EN-RAGE are up-regulated in subjects with TA. This study also demonstrates a positive correlation of RAGE and ENRAGE, in subjectswith TA for thefirst time. Our data is supported by other reports, which demonstrate that RAGE expression increases stably in certain pathological processes, and is associated with ligand-rich microenvironments [6,7]. In a previous study, we demonstrated that RAGE and EN-RAGE genes are augmented in non-diabetic CAD subjects and showed their positive correlation with the severity of disease [5]. Ligation of this receptor with its ligands activates the downstream signaling pathways such as NF-κB [10]. In addition, RAGE and EN-RAGE interactions could further induce the expression of adhesion molecules, migration and proliferation of leukocytes and augment cytokine release from the lymphocytes. Excessive expression of these genes at sites of inflammation may feasibly form a positive feedback loop that may further aggravate underlying inflammation. In corroboration to this, other reports in literature and our work have clearly demonstrated a potential participation of various cytokines, chemokines and MMPs in the pathophysiology of TA [3,8,9,11]. Significantly increased RAGE–EN-RAGE expression in TA further confirms a prevalent oxidative stress and inflammatory milieu in such a situation. Presence of various functional splice variants of RAGE is another important characteristic of this particular receptor. The production of endogenous secretory RAGE by alternative splicing may influence the actions of ligands on the full form of RAGE, located on the plasma membrane [12]. Finding increased RAGE mRNA levels in TA subjects, one

The purpose of this study was to estimate the effect of long-term exposure to lower plasma low-density lipoprotein cholesterol (LDL-C) on the risk of coronary heart disease (CHD).LDL-C is causally related to the risk of CHD. However, the association between long-term exposure to lower LDL-C beginning early in life and the risk of CHD has not been reliably quantified.We conducted a series of meta-analyses to estimate the effect of long-term exposure to lower LDL-C on the risk of CHD mediated by 9 polymorphisms in 6 different genes. We then combined these Mendelian randomization studies in a meta-analysis to obtain a more precise estimate of the effect of long-term exposure to lower LDL-C and compared it with the clinical benefit associated with the same magnitude of LDL-C reduction during treatment with a statin.All 9 polymorphisms were associated with a highly consistent reduction in the risk of CHD per unit lower LDL-C, with no evidence of heterogeneity of effect (I(2) = 0.0%). In a meta-analysis combining nonoverlapping data from 312,321 participants, naturally random allocation to long-term exposure to lower LDL-C was associated with a 54.5% (95% confidence interval: 48.8% to 59.5%) reduction in the risk of CHD for each mmol/l (38.7 mg/dl) lower LDL-C. This represents a 3-fold greater reduction in the risk of CHD per unit lower LDL-C than that observed during treatment with a statin started later in life (p = 8.43 × 10(-19)).Prolonged exposure to lower LDL-C beginning early in life is associated with a substantially greater reduction in the risk of CHD than the current practice of lowering LDL-C beginning later in life.

Background Left main disease (LMD) and three-vessel disease (3VD) have important prognostic value in patients with coronary artery disease. However, uncertainties still exist about their prevalence and predictors in patients with acute coronary syndrome (ACS) and also in patients with stable coronary disease. Thus the aim of this study was to perform an international collaborative systematic review and meta-analysis to appraise the prevalence and predictors of LMD and 3VD. Methods Medline/PubMed were systematically searched for eligible studies published up to 2010, reporting multivariate predictors of LMD or 3VD. Study features, patient characteristics, and prevalence and predictors of LMD and 3VD were abstracted and pooled with random-effect methods (95% CIs). Results 17 studies (22 740 patients) were included, 11 focusing on ACS (17 896 patients) and six on stable coronary disease (4844 patients). In the ACS subgroup, LMD or 3VD occurred in 20% (95% CI 7.2% to 33.4%), LMD in 12% (95% CI 10.5% to 13.5%), and 3VD in 25% (95% CI 23.1% to 27.0%). Heart failure at admission and extent of ST-segment elevation in lead aVR on 12-lead ECG were the most powerful predictors of LMD or 3VD. In the stable disease subgroup, LMD or 3VD was found in 36% (95% CI 18.5% to 48.8%), with the most powerful predictors being transient ischaemic dilation during the imaging stress test, extent of ST-segment elevation in aVR and V1 during the stress test, and hyperlipidaemia. Conclusions This meta-analysis demonstrated that severe coronary disease—that is, LMD or 3VD—is more common in patients with ACS or stable coronary disease than generally perceived, and that simple and low-cost tools may help in the selection of the most appropriate therapeutic approach.

Although there appears to be a role for statins in reducing cerebrovascular events, the exact role of different lipid fractions in the etiopathogenesis of cerebrovascular disease (CVD) is not well understood. A secondary analysis of data collected for the placebo arm (n = 2,078) of the Cholesterol and Recurrent Events (CARE) trial was performed. The CARE trial was a placebo-controlled trial aimed at testing the effect of pravastatin on patients after myocardial infarction. Patients with histories of CVD were excluded from the study. A Cox proportional-hazards model was used to evaluate the association between plausible risk factors (including lipid fractions) and risk for first incident CVD in patients after myocardial infarction. At the end of 5 years, 123 patients (6%) had incident CVD after myocardial infarction (76 with stroke and 47 with transient ischemic attack). Baseline non–high-density lipoprotein (HDL) cholesterol level emerged as the only significant lipid risk factor that predicted CVD; low-density lipoprotein cholesterol and HDL cholesterol were not significant. The adjusted hazard ratios (adjusted for age, gender, hypertension, diabetes mellitus, and smoking) for CVD were 1.28 (95% confidence interval [CI] 1.06 to 1.53) for non-HDL cholesterol, 1.14 (95% CI 0.96 to 1.37) for low-density lipoprotein cholesterol, and 0.90 (95% CI 0.75 to 1.09) for HDL cholesterol (per unit SD change of lipid fractions). This relation held true regardless of the level of triglycerides. After adjustment for age and gender, the hazard ratio for the highest natural quartile of non-HDL was 1.76 (95% CI 1.05 to 2.54), compared to 1.36 (95% CI 0.89 to 1.90) for low-density lipoprotein cholesterol. In conclusion, non-HDL cholesterol is the strongest predictor among the lipid risk factors of incident CVD in patients with established coronary heart disease.

The Ets proteins are a family of transcription factors characterized by an evolutionarily conserved DNA binding domain that controls key cellular processes. Prostate-derived Ets transcription factor (PDEF), a member of the Ets family, is reported to be present in tissues with high epithelial content, notably breast and prostate. However, the role of PDEF in cancer development is not fully understood. To gain insight into the molecular mechanisms associated with prostate cancer progression, we employed iTRAQ labeling followed by mass spectrometric (MS) analysis to identify candidate proteins that are differentially expressed in prostate cancer cells with or without PDEF. To this end, we overexpressed PDEF in PC3 human prostate cells using a tetracycline inducible system (Tet-On). Many differentially expressed proteins which play important roles in various cellular and biological processes were identified. Among them, stathmin (STMN), which is a microtubule (MT)-destabilizing protein, was found to be downregulated in multiple analyses. We demonstrated that re-expression of STMN reversed the antitumor properties of PDEF in PDEF-overexpressing PC3 cells. Using in vitro functional assays, we showed that STMN overexpression counteracted PDEF's effects against cell proliferation, colony formation and tumor migration. Similar results were further confirmed with the prostate cancer cell line CWR22rv1. In conclusion, many differentially expressed proteins were identified and STMN was found to be downregulated by PDEF. These results suggest that PDEF may inhibit prostate cancer progression by transcriptional downregulation of oncogenic STMN expression. Analyzing the association among differentially expressed proteins may provide a basis to better understand the molecular mechanisms underlying the process of cancer progression and development and further aid in designing therapeutics in the future.

stent thrombosis: strut coverage as a marker of endothelialization. Circulation 2007;115:2435–41. [4] Takebayashi H, Mintz GS, Carlier SG, et al. Nonuniform strut distribution correlates with more neointimal hyperplasia after sirolimus-eluting stent implantation. Circulation 2004;110:3430–4. [5] Turco MA, Ormiston JA, Popma JJ, et al. Polymer-based, paclitaxel-eluting TAXUS Liberte stent in de novo lesions: the pivotal TAXUS ATLAS trials. J Am Coll Cardiol 2007;49:1676–83. [6] TakanoM, Ohba T, Inami S, et al. Angioscopic differences in neointimal coverage and in persistence of thrombus between sirolimus-eluting stents and bare metal stents after a 6-months implantation. Eur Heart J 2006;27:2189–95. [7] YamamotoM, Okamatsu K, Inami S, et al. Relationship between neointimal coverage of sirolimus-eluting stents and lesion characteristics: a study with serial coronary angioscopy. Am Heart J 2009;158:99–104. [8] Takano M, Yamamoto M, Murakami D, et al. Lack of association large angiographic late loss and low risk of in-stent thrombus: angioscopic comparison between paclitaxeland sirolimus-eluting stent. Circ Cardiovasc Intervent 2008;1:20–7. [9] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.

Background and Aims C-reactive protein (CRP) serves not only as a biomarker for the risk of cardiovascular disease and underlying inflammation but also functions as an active mediator of atherosclerosis by promoting activation of endothelial cells and monocytes. Peroxisome proliferator activated receptor-gamma (PPAR-γ) transcription factor has been recognized to regulate the expression of many genes involved in inflammation, lipid metabolism and vascular remodeling. Therefore, in the present study we tried to explore the role of CRP as a possible mediator of atherosclerosis by determining its effect on PPAR-γ and its effector genes, i.e., liver X receptor-α (LXR-α) and matrix metalloproteinase-9 (MMP-9) in THP-1 cells. Methods Semi-quantitative RT-PCR was used to determine mRNA expression. Results CRP upregulates the expression of PPAR-γ and LXR-α at lower doses (5–25 μg/mL), which were further declined at higher doses (50–100 μg/mL). However, a dose-dependent increase was observed for MMP-9 expression. Atorvastatin (10–20 μM) was able to significantly accelerate the CRP-induced expression of PPAR-γ and LXR-α and attenuate MMP-9 expression. Conclusions For the first time we demonstrate that CRP modulates PPAR-γ and its effector genes and reinforces the mechanistic link of CRP as a possible mediator in atherosclerosis and also advocate atorvastatin as a therapeutic modality.

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The role of CRP as a mediator in atherosclerosis and inflammation is being investigated worldwide. In the present study, the effect of CRP on matrix metalloproteinases (MMP)-1, 2, 9, and their tissue inhibitor (TIMP-1) gene expression in THP-1 monocytic cell line was investigated. Specific mitogen activated protein (MAP) kinase (ERK, p38, and JNK) inhibitors were used to elucidate the signaling pathways involved. Effect of atorvastatin was determined in the presence of CRP on the expression of genes. Time and dose-dependent experiments were performed in the presence of CRP. The results showed that the treatment of THP-1 cells with 100 microg of CRP/ml/10(6) cells for 24 h enhanced the expression of MMPs and TIMP-1 genes significantly. CRP upregulated the expression of these genes via FcgammaRII and utilized ERK signaling pathway to transduce signals. Atorvastatin was able to significantly attenuate CRP-induced MMPs expression and augmented TIMP-1 gene expression significantly. In conclusion, CRP is not only a risk marker for vascular events, but also directly involved in the mechanisms leading to remodeling and destabilization of atherosclerotic plaque. Also, atorvastatin serves as potential therapeutic modality to curb these harmful events.

Studies are lacking in literature, which demonstrate the cumulative impact of certain soluble markers in predicting the severity of CAD. Serum hsCRP, MMP-9, TIMP-1 and sRAGE levels were measured in non-diabetic 100 angiographically proven CAD patients (Group I) and 40 non-diabetic subjects with coronary risk factors and without any lesions (Group II). Increased levels of serum hsCRP, MMP-9, TIMP-1 and decreased levels of sRAGE were observed in Group I as compared to Group II. Gensini score, a measure for severity of CAD was found to be positively correlated with serum hsCRP, MMP-9, TIMP-1 and negatively with sRAGE. Multivariate analysis revealed serum MMP-9, hsCRP, sRAGE and family history as predictors of severity of CAD with a cumulative sensitivity and specificity of 92% and 82%, respectively. Cumulative impact of these soluble markers, in addition to the established markers will contribute to improve the predictive value for the assessment of disease severity.

Multiple myeloma (MM) is an incurable malignancy of antibody secreting plasma B cells. The t(4;14) translocation is detected in 20% of MM and is associated with shortened patient survival. Although the t(4;14) is known to up regulate the MMSET proteins, its role in MM remains unclear. Previously, we identified a novel orphan box H/ACA class small nucleolar RNA (snoRNA), that is located within intron 19 of MMSET, and is expressed in MM cells harboring the t(4;14) translocation. H/ACA small RNAs are an evolutionarily conserved class of abundant noncoding RNAs (ncRNA) involved in a diverse range of processes including posttranslational modifications of functional RNAs, preribosomal RNA processing, and telomere maintenance, yet their contribution to human disease remains largely unexplored. In this study, t(4:14) positive and negative MM patient tumor cells were analyzed by RNA sequencing. This revealed a unique signature of up regulated genes involved in mitochondrial respiration and oxidative stress. Our hypothesis is ACA11 plays critical role in MM cell proliferation and cell transformation by increasing oxidative stress. We found that acute ACA11 overexpression leads to the increased oxidative stress in primary splenic B-cells, established myeloma cell lines, as well as embryonic fibroblasts. In particular, cells overexpressing ACA11 showed enhanced proliferation, significantly larger colony sizes in soft agar assays, and elevated ERK1/2 phosphorylation, a downstream consequence of oxidative stress. In addition, we found that the transcription factor nuclear factor erythroid-derived 2-related factor 2 (Nrf2), which regulates anti-oxidant signaling, dissociated from Keap1 and translocated to the nucleus, but failed to activate anti-oxidant downstream targets in ACA11 overexpressing cells. Furthermore, ACA11 up regulated TXNIP, which encodes an inhibitor of ROS scavenger thioredoxin. In conclusion, we propose that acute overexpression of ACA11 up regulates TXNIP and suppresses the ability of Nrf2 to induce target anti-oxidants genes, resulting in increased oxidative stress and cell proliferation. These changes may be critical events in the development and/or progression of multiple myeloma. Citation Format: Nitin Mahajan, Leonard B. Maggi, Michael H. Tomasson, Jason D. Weber. The multiple-myeloma associated snoRNA, ACA11 increases oxidative stress and cell proliferation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-298. doi:10.1158/1538-7445.AM2015-LB-298

Left main coronary artery disease carries a poor prognosis. The etiology of isolated and significant left main coronary artery (ILMCA) disease is not well understood. Studies so far were limited by small numbers. The authors identified 46 patients with ILMCA disease from their database over 10 years (group I) and compared them with 83 consecutive patients undergoing catheterization (group II). They also compared patients with ostial vs distal ILMCA disease. Group I represented 0.1% of catheterization patients. The demographic profile and atherosclerotic risk factor profile of the 2 groups as well as ostial and distal ILMCA disease were compared. This is the largest study of ILMCA disease. Risk factors for atherosclerosis were commonly seen. Nonatherosclerotic causes of ILMCA disease were not seen. This study suggests coronary atherosclerosis as the predominant cause of ILMCA disease. ILMCA disease is more common in women. Diabetes is more commonly associated with distal ILMCA lesion. There is a trend suggesting that ostial ILMCA lesion is more common in smokers and women.

Background Takayasu's arteritis (TA) is a chronic obliterative inflammatory disease. Inflammatory cell infiltration and destruction of the vessel wall in TA strongly suggest that cell mediated immunological mechanisms play an important role in the pathogenesis of this disease. Therefore, in the present study our aim was to focus on the role of chemokines and adhesion molecules in patients with Takayasu's disease. Methods Twenty-one patients with clinically defined TA and 21 healthy control volunteers were recruited by using the standard criteria. Patients with TA were divided into those with clear-cut clinically active or inactive disease based on vasculitis activity score. Results MCP-1 and hRANTES were significantly increased in patients with TA as compared to controls. MCP-1 and hRANTES values were reliably able to distinguish between patients with active disease vs. subjects in remission. sVCAM-1 levels remained unaltered between patients and controls. Conclusions C–C chemokines can be used as reliable markers/diagnostic tools in determining the activity of Takayasu's arteritis.

Background Elevated troponin I in the absence of angiographically visible coronary lesions is seen in up to 10–15% of those undergoing angiography for suspected coronary artery disease. This study aims to elucidate the etiology of elevated cardiac troponin I in patients with normal coronary arteries on angiography. Methods We identified 1551 (8.6%) patients with normal coronary arteries from our catheterization database of 17,950 patients from Jan 2000 to Jun 2004. Elevated troponin I levels were found in 217 (14%) of 1551 patients with normal coronary arteries. Of these 217 patients, 73 surgical patients were excluded, and the remaining 144 patients formed the study population. The study population was compared with age and gender matched patients with myocardial infarction and coronary artery disease (Group II). Results The patients with elevated cardiac troponin I (cTnI) with normal coronary arteries had significantly lower prevalence of atherosclerotic risk factors and significantly higher left ventricular ejection fractions. The cTnI in patients with normal coronary arteries was elevated due to a number of causes including tachycardia, myocarditis, pericarditis, severe aortic stenosis, gastrointestinal bleeding, sepsis, left ventricular hypertrophy, severe congestive heart failure, cerebrovascular accident, electrical trauma, myocardial contusion, hypertensive emergency, myocardial bridging, pulmonary embolism, diabetic ketoacidosis, chronic obstructive pulmonary disease exacerbation and coronary spasm. Conclusions Cardiac troponin I could be elevated in a number of conditions, apart from acute myocardial infarction, and could reflect myonecrosis. Acute myocardial infarction is a clinical diagnosis as the laboratory is an aide to, not a replacement for, informed decision making.

with advanced heart failure. J Am Coll Cardiol 2006;48:2485–9. [9] Okonko DO, Grzeslo A, Witkowski T, et al. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency: FERRIC-HF: a randomized, controlled, observerblinded trial. JACC 2008;51:103. [10] Beck da Silva L, Rohde LE, Clausell N. Etiology and management of anemia in patients with heart failure: how much iron is missing? Congest Heart Fail Jan-Feb 2008;14(1):25–30. [11] Chandler G, Harchowal J, Macdougall IC. Intravenous iron sucrose: establishing a safe dose. Am J Kidney Dis 2001;38(5):988–91. [12] Chertow GM, Mason PD, Vaage-Nilsen O, Ahlmen J. Update on adverse drug events associated with parenteral iron. Nephrol Dial Transplant 2006;21(2):378–82.

A55-year-old man presented to the emergency room (ER) with complaints of anorexia, feelings of being unwell and anuria from the previous day. He denied any chest pain, palpitations, dyspnoea on exertion or fever. He was recovering from a recent throat infection and had a past medical history of diabetes mellitus, hypertension and hypercholesterolaemia. He was pale-looking and his physical examination revealed hypotension (90/60 mmHg) and tachycardia. He appeared in mild respiratory distress. Examination of neck veins showed raised jugular venous pressure of 6 cm above the sternal angle. His chest was clear on auscultation and the intensity of heart sounds were diminished with no added sounds. He had a measured pulsus-paradoxus of 20 mmHg. His electrocardiogram showed diffuse low-voltage complexes with no evidence of electrical alternans. There were ST segment elevations in lateral leads with tall T-waves in anterior precordial leads suggestive of posterolateral myocardial infarction (Figure 1). Posterior changes were confirmed on a posterior electrocardiogram (Figure 2). Right-sided electrocardiogram failed to reveal any ST-T abnormalities suggestive of right ventricular infarction. The initial set of laboratory tests done in ER revealed high blood urea nitrogen (9.64 mmol/litre) and serum creatinine (150.28 μmol/litre). The first set of cardiac enzymes revealed high troponin I (23.05 μg/litre) with normal myoglobin and creatine kinase. An arterial line was placed that revealed pulsus-paradoxus of 20 mmHg. A Swan–Ganz catheter was placed and showed: right ventricle of 53/33 mmHg; right atrium of 28 mmHg; pulmonary artery of 50/32 mmHg; pulmonary capillary wedge pressure of 30 mmHg. The central venous pressure tracing showed complete obliteration of ‘y’ descent. Dopplerechocardiography was done. It showed mild-to-moderate pericardial effusion with possible thrombus overlying the right ventricular wall. Posterior and lateral walls were found to be hypokinetic. The patient underwent coronary angiography before emergency pericardiocentesis. Angiography revealed complete occlusion of the first obtuse marginal. Aortic-pulse tracing is shown in Figure 3. These pressure tracings were consistent with cardiac tamponade with a demonstrable pulsus-paradoxus of about 20 mmHg. Ventriculography was not performed because of a suspected subacute rupture of the myocardial wall. A cautious pericardiocentesis was performed. Examination of the pericardial cavity revealed 300 cm3 of blood clots. In the absence of an ongoing leak, a pericardial window was created and a drain was left in situ. The patient was dialysed once after the procedure. His haemodynamics improved significantly after surgery. He remained stable through the course of his stay in the hospital and was discharged 3 days after pericardiocentesis.

Sun et al. recently reported matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) as potential biomarkers for disease activity in Takayasu's arteritis (TA) in Chinese population [1]. Authors determined serum levels ofMMPs (MMP-3 and 9), tissue inhibitor ofMMPs (TIMP-1) and IL-6 in subjectswith TA and correlatedwith the disease activity of the disease. In a subgroup offifteenTA subjects they demonstrated that levels ofMMP-9 and IL-6 are able to predict the imagingoutcomeof thepatients with TA, but at the same time failed to notice any significant correlation between the pathological findings and the serum levels of MMP-9 and MMP-3 and IL-6. While reading this article, we found that the authors missed a few important studies to discuss in context to this particular field, where importance of IL-6 andMMPs-TIMP-1 has been established as potential biomarkers for this disease. Noris et al [2] in Italian population demonstrated a close relation of serum IL-6 with disease activity and suggested that it could contribute to vasculitic lesion in TA and could be relevant in the setting of therapeutic management of TA. In another study from Japan, Matsuyama et al [3] suggested that monitoring of circulating levels of MMP-2 as a helpful marker in diagnosing TA and those of MMP-3 and MMP-9 as disease activity markers might help provide adequate evaluation of treatment and guide therapeutic decision making for individual patients with TA. Our research group in India has also demonstrated importance of different MMPs (MMP-1, MMP-2, MMP-3, MMP-9 and TIMP-1) and their significant correlation with oxidative stress biomarkers (8-isoPGF2α and nitrite levels) in Takayasu's arteritis [4,5]. The etiopathogenesis of Takayasu's arteritis disease remains enigmatic, and various mechanisms such as post-infective, autoimmune, ethnic susceptibility and a genetic predisposition have been postulated [4,6]. As concluding remarks, we want to emphasize the fact that TA has been reported all over theworld with awide variation in its prevalence in different geographical regions. Moreover, it has been reported to cause different aortic lesion at different places in different countries [7]. Comparing and thoroughly analyzing the results from various studies reported worldwide will be of great help to provide a correct direction for future research on TA, as each and every researcher in this particular area is teaming to address the questionwhether any of thesemolecules can beused as amarker tomonitor the clinical course of the disease or to predict the disease exacerbations. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [8].

Numerous randomized trials have demonstrated that treatment with a statin reduces the risk of major cardiovascular events (MCE). We sought to quantitatively estimate the potential pleiotropic effect of statins by estimating the magnitude of this clinical benefit not related to the low-density

Objective To investigate the in vitro effects of atorvastatin on lipopolysaccharide (LPS)-induced gene expression in endometrial-endometriotic stromal cells. Design In vitro experimental study using flow cytometry, ELISA, semiquantitative reverse transcriptase polymerase chain reaction, and Western blot. Setting Postgraduate Institute of Medical Education and Research. Patient(s) Twenty-five women undergoing laparoscopy (n = 10) and laparotomy (n = 15). Intervention(s) Endometriotic cyst wall (group I) and endometrial biopsy (group II) collection. Main Outcome Measure(s) The endometrial-endometriotic stromal cells were isolated from ectopic (group I) and eutopic (group II) endometrium by established methods, cultured, and stimulated with LPS (1 μg/mL), followed by atorvastatin treatment in a time- and dose-dependent manner to investigate the effects of LPS on proliferation (Ki-67) and expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), receptor for advanced glycation end products (RAGE), extracellular newly identified RAGE binding protein (EN-RAGE), peroxisome proliferator activated receptor-γ (PPAR-γ), and liver X receptor-α (LXR-α) genes in endometrial-endometriotic stromal cells and on levels of insulin-like growth factor binding protein-1 (IGFBP-1) and 17β-E 2 in endometrial-endometriotic stromal cell culture supernatant. Result(s) Significant inhibition of Ki-67 and LPS-induced expression of inflammatory and angiogenic genes (COX-2, VEGF, RAGE, and EN-RAGE) was observed in atorvastatin-treated endometrial-endometriotic stromal cells. In contrast, a significant dose- and time-dependent increase in expression of anti-inflammatory genes (PPAR-γ and LXR-α) and levels of IGFBP-1 was observed after atorvastatin treatment in both the groups. However, atorvastatin treatment had no effect on 17β-E 2 levels in endometrial/endometriotic stromal cell culture supernatant. Conclusion(s) The data of the present study provide new insights for the implication of atorvastatin treatment for endometriosis in humans.