Scientific Program

Conference Series Ltd invites all the participants across the globe to attend Annual Conference on Atherosclerosis and Clinical Cardiology Philadelphia, Pennsylvania, USA.

Day 1 :

Keynote Forum

Sampath Parthasarathy

University of Central Florida, USA

Keynote: Do lipid peroxidation products contribute to atherosclerotic calcification?

Time : 10:10-10:40

OMICS International Atherosclerosis 2016 International Conference Keynote Speaker Sampath Parthasarathy photo
Biography:

Sampath Parthasarathy was instrumental in the development of the concept of oxidized LDL and its contribution to atherosclerosis, a major form of cardiovascular disease. He is currently at University of Central Florida as the Florida Hospital Chair in Cardiovascular Sciences and the Associate Dean of Research. Dr. Parthasarathy has published over 250 articles and has served on numerous editorial boards and NIH committees. He has been continuously funded by NIH and other agencies for over 30 years and he was awarded the distinguished service Award by the American Heart Association and by the American Association of Cardiologists of Indian Origin and from SASAT International. He is also the recipient of the prestigious van Deenen Memorial award for lipids and the Ranbaxy Award for excellence in cardiovascular research.

Abstract:

Background: Cardiovascular diseases, including atherosclerosis, are the leading cause of death in the United States. Atherosclerotic lesions are formed by deposition of lipids in the intima of arteries. Upon exposure to oxidative stresses, low-density lipoprotein (LDL) is converted to highly atherogenic oxidized LDL (ox-LDL) particles, which contribute to disease development and progression. Advanced disease stages may result in calcification of lesions. This calcification process is important, as it has been shown to be associated with stable plaques that are less prone to rupture. Calcification is present in lipid rich domains of lesions and correlates well with overall plaque burden. However, neither the composition of the mineralized calcium deposits nor its relationship to lipid peroxidation is known.rnMethods: In this study, the potential of lipid peroxide-derived lipophilic dicarboxylic acid (DCA, e.g. azelaic acid) to promote calcification upon exposure to vascular smooth muscle cells was tested. Using 13-Hydroperoxyoctadecadienoic acid (13-hydroperoxylinoleic acid, 13-HPODE) and thin-layer and gas chromatography–mass spectrometry we characterized the conditions where HPODE is decomposed to aldehyde product 9-oxo-nonanoic acid and its corresponding DCA azelaic acid (AZA).rnResults: HPODE treatment resulted in the cellular conversion to ONA and AZA as determined by GC-MS. Both free AZA and intracellular delivery of AZA via lyso phosphatidylcholine (lysoPtdCho) micelles induced calcification of aortic smooth muscle cells, as determined by Von Kossa and alizarin red staining. rnConclusion: These results demonstrate that DCAs may contribute to atherosclerotic calcification thus accounting for the latter’s relationship to plaque burden and association with lipids. This study also challenges the dogma that arterial calcification represents the deposition of calcium phosphate. Our future work aims to delineate the association of calcium with lipid rich plaques and lipid oxidation with calcification in animal and human atherosclerosis.rn

Keynote Forum

Yong-Jian Geng

University of Texas McGovern School of Medicine USA

Keynote: Vascular cell apoptosis and calcification in arteries with atherosclerotic hypertension

Time : 10:00-10:30

OMICS International Atherosclerosis 2016 International Conference Keynote Speaker Yong-Jian Geng photo
Biography:

In 1982 Dr. Yong-Jian Geng graduated from Suzhou Medical College, China. In 1994, he obtained doctoral degree of medical science from Goethenburg University, and then pursued his cardiology fellowship, and in 1995, was appointed as instructor of medicine at Harvard Medical School. In 1999, Dr. Geng joined the faculty of Schoo of Medicine, University of Texas Health Science Center at Houston. In 2000 he was appointed Director of the Center for Cardiovascular Biology and Atherosclerosis Research, and in 2001, he was named Director of Stem Cells and Heart Failure Research at Texas Heart Institute. Dr. Geng was promoted to Professor of Medicine in 2005.

Abstract:

Cellular accumulation, lipid deposition and connective tissue formation in the arterial intima characterizes the development of atherosclerotic plaques. However, the increased cell mass in the intima does not reflect the rates of cell growth and death. Over the long-lasting process of atherogenesis often for several decades, many plaque cells may undergo apoptosis, a form of programmed cell death. Atherosclerosis and hypertension are closely associated chronic arterial diseases. In many case, they co-exist and interplay, triggering the development of life-threatening complications, such as myocardial and cerebral infarctions. Increased apoptosis and phenotypic alteration of vascular cells occur in the arterial wall with various pathological conditions, including atherosclerosis and hypertension. Several molecular pathways contribute to the changes of cellular components in atherosclerotic lesions. Maintaining normal structure and shape of the blood vessels requires a balance between apoptosis and proliferation. During the pathogenesis of atherosclerosis and hypertension, vascular cells may become malfunctional or injured by various potentially harmful factors. Vascular smooth muscle cells exposed to pro-atherogenic and hypertensive factors are undergoing phenotypic changes, which transform the cells from contractile to synthetic styles. Two prominent pathological alterations are reduction of vascular cell survival and promotion of calcification. Those processes are regulated by an epigenetic process involved in expression of different epigenetic factors. Clarification of these pathways may aid development of novel therapeutic strategies to treat atherosclerotic hypertension, and its complications, including the acute coronary syndromes. The attenuation of apoptosis and calcifification increases the cellularity and reduces stiffness and vulnerability for rupture in the arterial wall.

  • Session 1 Atherosclerosis Therapeutics
Location: Philadelphia
Speaker

Chair

Aouatef Bellamine

Lonza Global Nutrition, USA

Speaker
Biography:

Aouatef Bellamine earned her Ph.D. in life science from the University of Sorbonnes in Paris, France some 20 years ago. She has an extensive experience at both academia at Vanderbilt University and the pharma/biotech in the field of metabolic diseases and Nutrition. She was part of the development and the launch of metabolic compounds at Bristol-Myers Squibb and was involved in the research around cardiovascular attributes of these compounds. She authored over 20 publications and chapter books in peer reviewed journals in lipid metabolism, endocrinology and nutrition. She is currently heading the research and clinical development at Lonza.

Abstract:

Trimethylamine N-oxide (TMAO) plasma levels have been associated with atherosclerosis development in ApoE-/- mice. To better understand the mechanisms behind this association, we conducted in vivo studies looking at the effect of TMAO on different steps of atherosclerotic disease progression. Male ApoE-/- mice transfected with human cholesteryl ester transfer protein (hCETP) were fed L-carnitine and/or methimazole, a flavin monooxygenase 3 (FMO3) inhibitor that prevents the formation of TMAO. Following 12 week treatment, L-carnitine and TMAO plasma levels, aortic lesion development, and lipid profiles were determined. High doses of L-carnitine resulted in a significant increase in plasma TMAO levels. Surprisingly, and independently from treatment group, TMAO levels inversely correlated with aortic lesion size in both aortic root and thoracic aorta. High TMAO levels were found to significantly correlate with smaller aortic lesion area. Plasma lipid and lipoprotein levels did not change with treatment nor with TMAO levels, suggesting that the observed effects on lesion area were independent from lipid changes. These findings suggest that TMAO slows aortic lesion formation in this mouse model and may have a protective effect against atherosclerosis development in humans.

G.M. Anantharamaiah

University of Alabama, USA

Title: Apolipoprotein E mimetic: From theory to therapy

Time : 11:50-12:15

Speaker
Biography:

G. M. Anantharamaiah is a Professor in the Department of Medicine since 1982.. He received his postdoctoral training at Ohio State University in Columbus, OH in 1979 and a research associate in 1982 before coming to UAB as a faculty. His research has focused on structure and function of plasma Apolipoproteins, Apo-A1 Structure and Function, Apo-E Structure and Function, Structure Of Apo-A-1 In Alzheimer Disease Research. He initiated studies of peptide mimetics of apolipoproteins A-I and E, both ov which are licensed to two different companies for further development as therapies for lipid-mediated inflammatory disorders. He has published more than 200 papers in this field of research.

Abstract:

Apolipoprotein E (apoE) has a dual-domain structure, with a four helix bundle containing the receptor binding region in the amino terminal domain and a carboxyl terminal lipid binding domain. Peptides derived from the LDL receptor (LDL-R) binding region of apoE have been studied by a number of groups, with the primary focus being on the binding of the peptides to LDL-R. Based on the dual-domain structure, a peptide was designed with the highly cationic residues 141-150 from human apoE (hE) covalently bound to the lipid-associating Class A -helical peptide 18A and the amino and carboxyl termini blocked with acetyl and amide groups, respectively. This peptide, called Ac-hE18A-NH2 (in clinical development as AEM-28), was found to have striking cholesterol- and triglyceride-reducing and anti-inflammatory properties. Unlike statin drugs and proprotein convertase subtilisin/kexin type-9 (PCSK-9) inhibitors, these properties exist even in the absence of a functional LDL-R, with cholesterol reduction being mediated by binding to heparan sulfate proteoglycans (HSPG). Ac-hE18A-NH2 is currently undergoing Phase 1a/1b clinical trials, and has shown acceptable tolerability and promising efficacy. Thus, this and similar peptides have great potential for treatment of statin-resistant conditions such as familial hypercholesterolemia and acute hypertriglyceridemic pancreatitis.

Speaker
Biography:

Dipak Ramji received his BSc (Hons) degree (Biochemistry) and his PhD from University of Leeds. This was followed by post-doctoral research at the EMBL (Heidelberg) and IRBM (Rome) with fellowships from the Royal Society and the EU. He joined Cardiff University in 1992 and is currently a Reader at Cardiff School of Biosciences. His research is focused on the impact of the immune and inflammatory responses on atherosclerosis with emphasis on the action of cytokines on macrophages. He has published over 80 peer-reviewed papers, reviews and book chapters. He is an Editorial Board member of 16 international journals.

Abstract:

Atherosclerosis, an inflammatory disorder of the vasculature and the underlying cause of myocardial infarction and cerebrovascular accident, is responsible for more global deaths compared to any other disease. Although a slight reduction in morbidity and mortality from this disease has been achieved recently because of pharmaceutical intervention and lifestyle changes, this is expected to change in the future due to global increase in obesity and diabetes. Current pharmaceutical therapies against atherosclerosis are associated with a marked residual risk for cardiovascular disease together with other issues such as side effects and patient-dependent efficacy. In addition, many pharmaceutical agents have recently proved disappointing at the clinical level (e.g. agonists of peroxisome proliferator-activated receptors, inhibitors against cholesterol ester transfer protein and phospholipase A2). It is therefore important to develop alternative therapies for the prevention and/or treatment of atherosclerosis. Interest in nutraceuticals as preventative/therapeutic agents in atherosclerosis has recently increased considerably and therefore necessitates an in-depth understanding of their actions together with the underlying mechanisms. We have recently investigated the effects of several nutraceuticals, including hydroxytyrosol and dihomo-gamma-linolenic acid, on several key monocyte/macrophage processes associated with atherosclerosis (e.g. monocytic migration, macrophage polarization, foam cell formation, activation of inflammasome and production of reactive oxygen species). These will be presented in the context of current therapies and those that are being developed.

Speaker
Biography:

Renata’s degree is Agriculture Engineering, although she was always involved with Food Technology and more recently with Nutrition and Atherosclerosis, wich was her main focus on her doctorate program. Renata has completed her PhD at the age of 45 years old from Faculty of Medical Sciences, University of São Paulo, Brazil. She completed his Master’s degree at Faculty of Pharmaceuticals Sciences, University of São Paulo, where she developed her work at the Lipid Laboratory. She has 5 years of experience in basic research development involving animal modes of dyslipidemia. And also 5 years of experience with basic research in food science and technology. She has 5 papers published in well know research jounals. She is living in Pennington, New Jersey, since 2013.

Abstract:

The plasma cholesterol-reducing effect of phytosterols is well recognized and they are considered important adjuncts in the treatment of moderate hypercholesterolemia. However, studies have shown conflicting results regarding the efficiency of phytosterols in the prevention of atherosclerosis. In addition, studies showed that the increase in its plasma concentration is positively correlated to the risk of atherosclerosis. In order to elucidate its action on these parameters, the objective of this study was to evaluate the effects of phytosterol supplementation in the development of atherosclerosis in LDL receptor knock-out mice (LDLr -KO). The animals were fed during 16 weeks with high fat diet (40 % of calories as fat), supplemented (PS group, 2%, n = 10) or not (Control, n = 10) with phytosterol. Plasma and liver concentrations of cholesterol, triglycerides, PS (β - sitosterol, campesterol and lathosterol) were evaluated. In the aorta of the animals, the concentrations of total cholesterol, free cholesterol, cholesterol ester and PS, besides macrophage and lipids infiltration were determined. The mRNA expression of genes involved in cholesterol efflux and influx (ABCA1, ABCG1, LOX1 and CD36) were evaluated, in peritoneum macrophage, which resemble those present in the artery. As expected, PS supplementation induced increasing plasma concentration of campesterol and β-sitosterol and reducing cholesterol plasma concentration. The content of total cholesterol in the artery was lower in PS group animals however did not differ between the free and ester forms. Artery PS concentrations did not differ between groups. The lesion area in the PS group was lower than in the control group. PS supplementation induced reduction in mRNA expression of ABCG1, not affecting the expression of other genes studied in artery. Conclusion: The findings of this study demonstrate that the elevation of plasma PS concentration did not induce its accumulation in the arterial wall and prevented the development of atherosclerosis.

Break: Lunch Break: 13:05-14:00
  • Workshop on Apolipoprotein E: A therapeutic for atherosclerosis and CVDs
Location: Philadelphia
Speaker

Chair

G M Anantharamaiah

UAB Medical Center, USA

Speaker
Biography:

Robert L. Raffai earned a PhD from the University of Ottawa and pursued postdoctoral studies at the J. David Gladstone Institutes with Drs. Karl H. Weisgraber and Robert W. Mahley. He has published more than 25 papers on the topic of apolipoprotein metabolism and its influence of atherosclerosis. More recently, his laboratory has reported the first evidence that apoE regulates microRNA controlled NF-kB activation in macrophages and monocytes to suppress atherosclerosis in mice with hyperlipidemia. More recent studies from the laboratory uncovered evidence that apoE regulates the microRNA content and anti-inflammatory capacity of exosomes secreted by macrophages.

Abstract:

Monocytes and macrophages participate in the process of atherosclerosis. Although generally believed to be culprits of atherosclerosis, results of recent studies including from our laboratory have shown that subsets of monocytes and macrophages can suppress and even reverse atherosclerosis. An important feature of such protective monocytes and macrophages include the expression of the ApoE gene. Findings from our lab uncovered that ApoE expression causes an increase in levels of cellular microRNA that suppress NF-kB activation in monocytes and macrophages and thereby atherosclerosis in hyperlipidemic mice. Among the upregulated microRNA include miR146a. Furthermore, we reported that a systemic delivery of miR146a in lipid microparticles can suppress systemic inflammation and atherosclerosis in hyperlipidemic mice. In more recent studies, we explored whether apoE expression by monocytes and macrophages modulates miRNA content in exosomes to suppress atherosclerosis via their communication to cells of the immune system and vascular wall. To this end, exosomes were isolated from cultured bone marrow derived macrophages (BMDM) harvested from wildtype (WT) and ApoE deficient (ApoE-/-) mice. An absence of ApoE expression in BMDM resulted in a 30% increase in the secretion of exosomes with an average size of 85 nm. Such ApoE-/- exosomes were less effective than WT exosomes in reducing IL-6 mRNA expression in cultured endothelial cells exposed to TNF-alpha. Ongoing sequencing studies reveal major changes in the microRNA content of WT and ApoE-/- exosomes. Future studies will test the hypothesis that WT-BMDM derived exosomes can communicate protective microRNA signaling to cells of the immune system and vascular wall to suppress inflammation and atherosclerosis in mice with hyperlipidemia.

G.M. Anantharamaiah

UAB Medical Center, USA

Title: Rational design of apolipoprotein E mimetic peptides

Time : 14:00-14:25

Speaker
Biography:

G. M. Anantharamaiah is a Professor in the Department of Medicine since 1982.. He received his postdoctoral training at Ohio State University in Columbus, OH in 1979 and a research associate in 1982 before coming to UAB as a faculty. His research has focused on structure and function of plasma Apolipoproteins, Apo-A1 Structure and Function, Apo-E Structure and Function, Structure Of Apo-A-1 In Alzheimer Disease Research. He initiated studies of peptide mimetics of apolipoproteins A-I and E, both ov which are licensed to two different companies for further development as therapies for lipid-mediated inflammatory disorders. He has published more than 200 papers in this field of research.

Abstract:

Apolipoprotein (apo) A-I and apoE possess multiple tandem lipid-associating amphipathic helical domains. Both apoA-I and apoE possess anti-atherogenic and anti-inflammatory properties. While apoA-I possesses several 11-mer and 22-mer tandem amphipathic helical domains punctuated by a Pro, apoE has two domain structure with a four helix bundle at the N-terminus linked to a long amphipathic helical domain of 57 residues in length. As a first step to support the lipid association function of the amphipathic helix, we first designed an 18 residue peptide DWLKAFYDKVAEKLKEAF (18A), a sequence which has no homology to any of the apolipoproteins but was able to form peptide:lipid complexes, similar to apo A-I. This and several other analogs were therefore named as apoA-I mimetic peptides. While administration of analogs of this peptide were able to inhibit atherosclerosis in several mouse models, there was no change in plasma cholesterol. Since apoE is known to clear plasma cholesterol via the alternate heparan sulfate proteoglycan (HSPG) pathway, we added the HSPG binding domain of apoE from several species to the lipid associating peptide 18A. Thus the 10 residue pepide 141-150 from human apoE sequence (LRKLRKRLLR) was covalently linked to 18A to obtain Ac-hE18A-NH2. This and analogs with HSPG binding domains from other species were all able to associate with LDL and VLDL to alter electrophoretic mobility. Peptide-containing VLDL and LDL were rapidly taken up and degraded by fibroblasts and HepG2 cells. The uptake and degradation was inhibited by treatment of cells with heparinase/heparitinase. These results suggest that the peptide analogs, analogous to apoE, cleared atherogenic lipoproteins via the HSPG pathway. This marked the beginning of the design of apoE mimetic peptides and recently several more effective peptides have been designed. The abilities of these analogs to reduce plasma cholesterol in several dyslipidemic animal models will be discussed in other two talks.

Speaker
Biography:

C. Roger White is a Professor of Medicine in the Division of Cardiovascular Disease at the University of Alabama at Birmingham (UAB). He received his doctoral training in the Department of Physiology and Biophysics at the University of Illinois at Urbana-Champaign. White went on to pursue postdoctoral studies in the Vascular Biology and Hypertension training program situated in UAB’s Cardiology Division. He subsequently joined the faculty in the Division of Cardiovascular Disease in 1993. Dr. White is a Fellow of the American Heart Association Council for High Blood Pressure Research and the American Physiological Society Cardiovascular Section.

Abstract:

ApoE plays an important role in the regulation of plasma cholesterol and atherogenic lesion formation in animal models of atherosclerosis. While apoE represents a potentially important therapeutic target for the treatment of lipid disorders, there are no specific therapies that increase circulating levels of the apolipoprotein. ApoE mimetic peptides containing a lipid-associating domain and a putative apoE receptor binding sequence have been shown to interact with macrophages and hepatocytes to mediate cholesterol efflux and clearance, respectively. Subsequent studies showed that a single bolus injection of the apoE mimetic peptide Ac-hE18A-NH2 in Watanabe Heritable Hyperlipidemic Rabbits reduced circulating VLDL and LDL cholesterol for time periods up to 24 hrs. The reduction in VLDL was associated with the rapid clearance of triglycerides and an increase in plasma paraoxonase 1 activity. Chronic administration of the peptide similarly reduced cholesterol in both LDL receptor null and apoE null mice and prevented the progression of aortic lesions. Collectively, these results indicate that Ac-hE18A-NH2 exerts anti-atherogenic effects in the absence of apoE and functional LDL receptors. Recent studies demonstrate that Ac-hE18A-NH2 also reduces plasma glucose and insulin levels in sucrose-fed mice, a model of Type 2 diabetes. Mechanisms by which the peptide attenuates hyperglycemia are currently under investigation.

Break: Networking & Refreshments Break: 15:15-15:30

Dennis I. Goldberg

LipimetiX Development, Inc.,, USA

Title: Clinical development of apolipoprotein E mimetic peptides

Time : 15:15-15:55

Speaker
Biography:

Dennis I. Goldberg has 30 years of experience in the pharmaceutical and biotechnology industries, ranging from drug discovery at a Fortune 25 company to chief executive officer of “virtual” biotechnology companies. Goldberg has served as president, CEO and Founder of Transport Pharmaceuticals, Inc., President, CEO and Founder of neXus therapeutics, inc., a biotechnology management and consulting company, President, CEO and Director of BZL Biologics, a company developing monoclonal antibodies for the treatment of prostate cancer. The BZL antibody technology was licensed by Millennium Pharmaceuticals (NASDAQ:MLNM). Dr. Goldberg was President, CEO and co-Founder of Talaria Therapeutics, which developed the Large Unilamellar Vesicle (LUV) technology. Talaria Therapeutics was acquired by Esperion Therapeutics (NASDAQ:ESPR) less than two years after its formation. Goldberg was also Vice President of Product development and regulatory Affairs at GelTex Pharmaceuticals (NASDAQ:GELX), where he was responsible for all biological and clinical development activities at the company, leading to the approval of RenaGel® and WelChol®. He was also co-Founder of Transcend Therapeutics, a spin out of Clintec Nutrition Co. (a joint venture between Baxter and Nestle), where he was Vice President of Research and Development, and Science Coordinator for the Atherosclerosis Research Program at Pfizer Central Research. Goldberg holds a Ph.D. in Physiology and Biochemistry from Temple University and received post doctoral training at the University of Pennsylvania and at the Specialized Center of Research on Atherosclerosis, University of California, San Diego. He is a Fellow of the American Heart Association. He has published extensively in basic and clinical sciences and is the inventor on fifteen U.S.A patents.

Abstract:

AEM-28 (hE18A), the prototype 28 amino acid Apolipoprotein E mimetic is being developed for the treatment of refractory dyslipidemias and acute coronary syndrome. As part of the preclinical pharmacology program, AEM-28 was tested in cynomolgus monkeys to examine the effect of the peptide in a model with normal apo E expression and functionality. The monkeys were fed a high-fat and cholesterol diet that raised their cholesterol to 325 mg/kg. The monkeys were treated in an ascending dose protocol with 3, 6 or 12 mg/kg, biweekly. The animals were maintained on the high-fat and cholesterol diet throughout the study and recovery period following each dose. A single infusion of AEM-28, 12 mg/kg, decreased cholesterol to 100 mg/kg within 24 hours. Total cholesterol in the cynos remained 25% below baseline one week after infusion of AEM-28, despite continuation of the experimental diet. This resulted in a dramatic decrease in artery wall cholesterol exposure. AEM-28 was tested in Phase 1/2a clinical trials, demonstrating dose dependent decreases in VLDL cholesterol and TG of more than 70% within 1 hour of infusion. The 3.54 mg/kg peptide dose decreased fasting TG from 140 mg/dl to 32mg/dl and VLDLc decreased from 32 mg/dl to 8 mg within 1 hour. VLDLc and TG decreases were identical after each of three doses administered in the Phase 2a study, indicating the absence of neutralizing antibody formation. AEM-28-14, is a novel, second generation peptide that is 4X more potent than the prototype peptide in animal models. A new formulation has increased the NOAEL dose in animals 5X, potentially increasing the therapeutic window 20X. LipimetiX plans to move AEM-28-14 into the clinical in the first half of 2017.

  • Young Research Forum
Location: Philadelphia
Speaker

Chair

Dennis I. Goldberg

LipimetiX Development, Inc., USA

Speaker
Biography:

Perry Fisher is an Internal Medicine resident at the Mount Sinai Beth Israel Medical Center in New York. Born and raised in Queens, New York, Fisher attended an accelerated B.S./ M.D. program at the Sophie Davis School of Biomedical Education. He completed his clinical medical school training at Albany Medical College. Along the way, Fisher performed clinical research, presented at multiple conferences and lectures, published works, and amassed several awards honoring his work. Fisher now practices inpatient medicine at Beth Israel Hospital, and maintains outpatient privileges at the Ryan NENA Community Health Center – serving the underserved population of New York City’s Lower East Side. He has a passion for the art of Cardiology, and aspires to specialize in Cardiovascular Medicine.

Abstract:

Abnormalities of aortic valve morphology and function comprise the most common cardiac valvular lesions. Of these, severe aortic stenosis (SAS) poses a particularly eminent burden, especially in the elderly population. Though SAS classically presents with echocardiographic findings of a valve area ≤1.0 cm2 and a transvalvular pressure gradient ≥40 mmHg, variants exist. One example of this is low-flow low-gradient (LF-LG) SAS; in which a reduced transvalvular gradient present as a result of myocardial remodeling-related restrictive physiology and a subsequent reduced left ventricular ejection fraction. Treatment of patients with LF-LG SAS depends greatly on findings of dobutamine stress echocardiography – both to differentiate true, SAS from pseudo-AS, and to gather prognostic information in determining candidacy for valve replacement. Dobutamine echocardiography is a time and labor intensive test with risks and side effects to the patient. Postextrasystolic potentiation (PesP), the phenomenon of contractility augmentation following a premature ventricular contraction, can provide hemodynamic information to arrive at appropriate diagnoses of SAS. These post-systolic beats tend to match those seen with dobutamine. Therefore, they may provide similar prognostic information as has been validated in ischemic cardiomyopathy. We are presenting a series of seven patients, which provides experiential evidence of feasibility in this testing modality. Further investigation is needed to validate the hypothesis that PesP can be utilized in place of dobutamine stress testing in assessing severity of aortic stenosis in LF-LG scenarios.

Speaker
Biography:

S Jamuna has completed her MPhil in Biochemistry and joined PhD under the guidance of Dr. S Niranjali Devaraj, Department of Biochemistry, Guindy campus, University of Madras, India. She has an excellent knowledge of Bioinformatics and has published five papers in reputed journals.

Abstract:

Background: The regulation of lipid metabolism via autophagy in diabetes mellitus and obesity has been trending in the recent years. However, focus is required for atherosclerosis which develops due to lipid accumulation in the vessel walls. This study has been designed to explore the vital role of autophagy and its relationship with lipid metabolism in OxLDL induced foam cells. In this study, autophagy was induced by Oligomeric proanthocyanidins in OxLDL induced foam cells. Method: Foam cell formation was evaluated by Oil red O and Nile red staining. Accumulation of lipid droplets was confirmed by mRNA analysis of perilipin. Autophagic activity was determined by mRNA and protein expression. LC3b and p62 gene expression was examined by RT-PCR. The protein expression of LC3b, p62 and ATG5 was determined using Western blot analysis. Intracellular cholesterol and triglyceride levels in foam cells were quantitatively measured by enzymatic colorimetric assays. Lysosomal acid lipase levels were quantified spectroflourimetrically. Results: OxLDL induced macrophage derived foam cell showed increased accumulation of lipid droplets which was confirmed by Oil red O and Nile red staining. Oligomeric proanthocyanidins decrease intracellular cholesterol and triglyceride levels, increase lysosomal acid lipase activity, whereas the OxLDL induced foam cells exhibit increased accumulation of lipid droplets via overexpression of perilipin protein. Overexpression of LC3b and ATG5, and reduced expression of p62 are marker of autophagic flux. Conclusion: OxLDL-induced foam cells undergo autophagy upon treatment with Oligomeric proanthocyanidins.

Speaker
Biography:

Ram Jagannathan has completed his PhD in Clinical Medicine (Research) from Imperial College, London and presently pursuing his postdoctoral studies from NYU Langone Medical Center. He has published 13 papers in reputed journals (Lancet Diabetes and Endocrinology, Diabetes Care and the Endocrine) and serves as an ad hoc reviewer for Acta Diabetologica. Senior author of this report (Ann Marie Schmidt) lab discovered RAGE pathway. She is a distinguished scientist with lots of accolades and published >250 articles.

Abstract:

The accumulation of advanced glycation end products (AGEs) and their chief cell surface receptor (RAGE), has been implicated in the development and progression of diabetic complications, particularly nephropathy and cardiovascular disease. Although sRAGE and esRAGE are associated with chronic kidney disease (CKD), no studies have assessed the effectiveness of behavioral modification with changes in soluble levels of RAGE (sRAGE and esRAGE). The objective of this pilot study is to assess the impact of a technology-supported behavioral intervention on sRAGE and esRAGE. The samples are derived from the two ongoing randomized controlled trials (n=17). Overweight individuals with CKD (stages 1 to 4) with concurrent type 2 diabetes (T2D) are engaged with multiple behavior changes for 3-6 months. The multiple behavior changes includes: restriction of dietary energy, sodium and phosphate additive intakes, and increased physical activity. Intervention groups included: a) usual care; b) social cognitive theory (SCT)-based counseling c) self-monitoring; and d) SCT-based counseling plus self-monitoring. The interventions were delivered remotely using iPads, which were provided to participants. Measurement of sRAGE and esRAGE was carried out at baseline and during follow-up using conventional ELISA. For this interm analysis, we have combined the SCT and self-monitoring groups (b and c) due to small numbers. The mean age was 63.3± 9.0 years, and the samples comprised mostly of caucassian men (>75%). The mean body mass index was 34.3 ± 5.4 Kg/m2. At the end of the follow-up, we have shown that the intervention was associated with changes in sRAGE (P=0.2) and esRAGE (P=0.03). This is the first report to our knowledge which reveales an association of multi-component behavior intervention strategies with changes in plasma levels of sRAGE and esRAGE.

Rajbir Sidhu

Mount Sinai Beth Israel USA

Title: Giant obstructive left atrial myxoma: Case Report

Time : 16:55-17:15

Speaker
Biography:

Rajbir Sidhu is a resident in Internal Medicine at Mount Sinai Beth Israel Hospital. He completed his undergraduate degree at UCLA in Physiological Science before completing is MD at Drexel University College of Medicine.

Abstract:

Primary cardiac tumors have a frequency of .02%. Comparatively, metastatic involvement of the heart is 20 times more common. Myxomas are the most common primary cardiac tumor with approximately 80% originating in the left atrium. Here they grow into the atrial lumen causing nonspecific symptoms secondary to blood flow obstruction. We present a 74 year-old female with chief complaint of worsening dyspnea on exertion associated with vague chest discomfort of few months. She demonstrated no acute distress, but bibasilar crackles were present on lung exam. In 2011, TTE showed a cardiac mass; however, she was lost to follow up until this presentation. Given her previous imaging and worsening symptoms, she was referred to our hospital for evaluation. Chest x-ray showed small bilateral pleural effusions and bibasilar segmental atelectasis. Repeat TTE revealed a 7cm atrial myxoma; mobile on stalk with partial obstruction of left atrial inflow to left ventricle, causing functional mitral stenosis. Subsequently, surgical excision of the mass was performed with frozen section confirming the diagnosis of atrial myxoma. Post-procedure hospital course was uneventful and she remained asymptomatic at 3 month follow up. Primary left atrial myxomas can present without the classic “tumor plop” sign on physical exam. As such, clinical suspicion must be high when patients present with vague chest symptoms. Given the risk of embolization and worsening left ventricular inflow, prompt resection of the tumor is paramount. 25% of patients develop atrial arrhythmias after removal, and myxoma recurrence is between 2-5%. Therefore, follow up care is important.