Day 1 :
Keynote Forum
Veena Dhawan
Postgraduate Institute of Medical Education and Research, India
Keynote: Novel strategies to encounter inflammation and ER stress in coronary artery disease
Biography:
Abstract:
Atherosclerosis is the underlying cause of coronary artery disease (CAD) and a disease of multifactorial etiology. Recent investigations in atherosclerosis have been focused on inflammation and endoplasmic reticulum (ER) stress, providing new insights into the mechanism of the disease. Keeping in view the multifactorial aspects of this disease, novel strategies are urgently needed not only for identification of novel biomarkers, but also to search for remedies for prevention and treatment of this disease. C-reactive protein (CRP) is reported to be a biomarker of inflammation in CAD and is shown to actively contribute to the disease pathology. Our data from in vitro studies provided substantial evidence that MMP-TIMP and RAGE-EN-RAGE interactions significantly contribute to the pathophysiology of coronary artery disease. CRP was found to play a potential role in the induction, amplification, and prolongation of inflammatory response in atherosclerosis via modulating these genes and atorvastatin showed the potential to curb the deleterious effects of CRP. However, it is evident that besides use of several drugs like statins, inflammation persists in CAD patients. Therefore, we conducted studies with Terminalia arjuna (TA), a medicinal plant with a wide variety of applications in traditional medicine and referred to as a cardiotonic in Ayurvedic system of medicine. Evidence in literature demonstrates that TA like atorvastatin possesses pleotropic properties. Studies carried out in our laboratory have clearly demonstrated its anti-inflammatory and antithrombotic properties both in vitro as well as in vivo and in experimental animals. Expression of inflammatory genes eg. was found to be significantly reduced in vitro in a dose and time-dependent manner by Terminalia arjuna. Using a Systems Biology approach, observations of the in vitro study were further validated in a randomized, placebo-controlled, double-blind clinical trial in subjects with stable CAD who received either placebo or T. arjuna (500 mg twice a day; Himalaya) and were followed up to 6 months. TA was shown to attenuate inflammation and played a pivotal role in modulation of both cellular and humoral immunity. Chronic ER stress is implicated in the pathophysiology of atherosclerosis and is found to be associated with apoptosis. Research work in our lab demonstrated that TA specifically targeted early foam cell apoptosis via activation of unfolded protein response pathway. The data from our studies suggests use of a multipronged approach using novel therapies in terms of combination/ adjuvant therapy in clinical studies utilizing indigenous resources of medicinal plants to prevent/treat complex disorders such as CAD.
Keynote Forum
Khatijah Lim Abdullah
University of Malaya, Malaysia
Keynote: Clinical decision-making styles and critical thinking skills among general care nurses in Malaysia
Biography:
Khatijah Lim Abdullah has completed her Doctorate from the University of Southampton UK. She is currently a Professor in Nursing in University of Malaya, Malaysia and Vice President for Qualitative Research Association Malaysia. She has published more than 50 papers in reputed journals and is presently the Chief Editor for Malaysian Journal of Qualitative Research.
Abstract:
The aim of this study is to assess the relationships between critical thinking skills and types of clinical decision-making among general care nurses in Malaysia. This quantitative descriptive correlational study was conducted in nine public hospitals from Peninsular Malaysia. Five hundred and forty nine nurses recruited via multistage cluster sampling, completed the demographic data questionnaire, Health science reasoning test (HSRT) and 24-item Nursing Decision-making instrument (24-NDM). The results of the study show that nurses’ average HSRT score was 13.8±3.4 which meant the majority of them failed to manifest critical thinking skills. In addition, the results show that 65.2% of the nurses studied were more inclined in making quasi-rational decisions, with 24.6% inclined towards analytical-systematic decisions, whereas only 10.2% displayed intuitive-interpretive decisions (
=268, df=2, p<0.001). With multinomial logistic regression, only education qualification is significantly associated with the nurses’ critical thinking score, whereas years of working experience and education qualification significantly predicted types of clinical decision nurses made (p<0.001). Finally, there is significant positive relationship between critical thinking skills and clinical decision-making, which accentuates the positive results yielded from previous studies. This finding provides further evidence that critical thinking and clinical decision-making are both interrelated. Since clinical decision-making cannot be easily taught in nursing curricula, cultivating critical thinking among nursing students perhaps is the right remedy for producing future nurses who can make effective clinical decisions.
Keynote Forum
Normunds Sikora
Children’s University Hospital, Latvia
Keynote: The proper delivery pressure for cardioplegic solution in neonatal cardiac surgery – an investigation of biomechanical and structural properties in neonatal and adult coronary arteries
Biography:
Normunds Sikora has completed his Residency in Cardiac Surgery in 2008. Afterwards, he finished his PhD in Riga Stradins University. He has done efforts to improve the quality of cardiopulmonary bypass in cardiac surgery in Latvia working as Cardiac Surgeon and Specialist in cardiopulmonary bypass in Clinic for Pediatric Cardiology and Cardiac Surgery, Children’s University Hospital, Riga, Latvia. He is also an Assistant Professor in Riga Stradins University, Department of Surgery. He has established Latvian Society of Cardiopulmonary Bypass being its President currently. He is a National Delegate in European Board of Cardiovascular Perfusion. He has established National Education Program in Cardiovascular Perfusion being its Director currently. He has over 10 papers in different local and international medical journals.
Abstract:
Introduction: One of important issues in pediatric cardiac surgery is myocardial protection. When cardioplegic solution is injected into coronary arteries with a pump to ensure myocardial protection, it is necessary to determine the correct delivery pressure to avoid damage of the heart.
Methods: We investigated 12 coronary artery specimens without cardiac pathology retrieved from autopsies of neonates 9.3±9.7 days old and weight 3.99±0.7 kg and compared them to seven adult specimens with no detected atherosclerosis. Specimens were pressurized from 0 to 200 mmHg with the step of 20 mmHg, while maintaining the length of the sample in situ. Structural damages were investigated afterwards with light microscopy and immunohistochemistry.
Results: There was a rapid increase of strain until the inner pressure reached 80-100 mmHg, whilst the increase of stress in the wall of neonatal coronary arteries was less rapid. When the internal pressure exceeds 100 mmHg, the strain of the arterial wall increases much slower, but the wall stress and modulus of elasticity begin to increase rapidly - the structural elements of the arterial wall have been straightened and possible damage may appear. Results were compared with biomechanical properties of arterial wall of adults and differences had been found. Morphologic examination of tensile properties revealed prominent affection of the vascular wall of neonates with accentuated redistribution (loosening) of medial myocytes and adventitial vasa vasorum after being pressurized with the inner pressure of over than 100 mmHg.
Conclusions: Our experimental results show that the delivery pressure of the cardioplegic solution in neonatal coronary arteries should not exceed 100 mmHg. A raised inner pressure may increase the risk of structural damage of the vascular wall leading to the injury of myocardium.
- Heart Disease | Molecular Cardiology | Cardiovascular Medicine | Heart Failure | Arrhythmias | Pediatric Cardiology | Diabetes and Cardio-metabolic Diseases | Pediatrics | Nursing Education & Research
Location: Hotel Novotel Amsterdam Schiphol Airport - Amsterdam, Netherlands
Chair
Normunds Sikora
Children’s University Hospital, Latvia
Co-Chair
Khatijah Lim Abdullah
University of Malaya, Malaysia
Session Introduction
Cindy Rodrigues Cleto
Newcastle University, UK
Title: Defective cilia in endocardial derived cells; A cause for congenital heart defects?
Biography:
Cindy Rodrigues Cleto is a sixth year Medical Student at the University of Liverpool, UK. She completed an MReS in Cardiovascular Science at the University of Newcastle where she carried out this research.
Abstract:
Introduction: Primary cilia on endocardial cells could prove to be a cause of congenital heart defects. Endocardial cells mainly contribute to the outflow tract (OFT) and atrioventricular (AV) endocardial cushion; later developing into the four heart valves. Knocking out IFT88 creates abnormal primary cilia and in turn causes cardiac malformations.
Aims: The aims of this study were to establish the spatiotemporal expression of primary cilia on endocardial derived cells; and by using an IFT88 mouse model, to discover if defecting to the primary cilia in endocardial derived cells causes an abnormal cardiac phenotype?
Methods: For the spatiotemporal expression of primary cilia, Tie2Cre positive mouse embryos of age’s e10.5-e12.5 were stained with anti-green fluorescent protein and acetylated tubulin to show the endothelial cells and primary cilia respectively. For the IFT88 mouse model, three mutants were collects at e15.5; two were hematoxylin and eosin stained to look at histology and one was stained with acetylated tubulin to show any defect in the primary cilia.
Results: The spatiotemporal expression of primary cilia mainly highlighted that there is an abundance of cilia in the OFT and AV endocardial cushions at e10.5 and e11.5 but this significantly drops by e12.5. The IFT88 mouse model showed that knocking out IFT88 significantly decreases the number of primary cilia in mutants, causing cardiac malformations including atrio-ventricular septal defects and dysplastic mitral and tricuspid valves.
Conclusion: Primary cilia are present in the endocardial derived cells at earlier time points. Knocking out IFT88 does produce defective cilia that lead to cardiac malformations.
Veena Dhawan
Postgraduate Institute of Medical Education and Research, India
Title: Aberrant DNA methylation of M1-macrophage genes in coronary artery disease
Biography:
Veena Dhawan has completed her PhD from PGIMER and did Post-doctoral Research at Minneapolis USA and Postgraduate Institute of Medical Education and Research, Chandigarh, India. At present, she is working as a Professor in the Department of Experimental Medicine and Biotechnology at PGIMER a National Institute of repute. She has published around 90 papers in reputed journals and written around seven book chapters.
Abstract:
Macrophage heterogeneity within atherosclerotic lesions has attracted much interest owing to the importance of balance between M1 and M2 population. Though, it remains unknown how macrophage heterogeneity is regulated. Moreover, the regulation of macrophage polarization and activation also involve DNA methylation. However, it remains unknown which genes are directly regulated by DNA methylation. The aim of the study was to assess the gene-specific promoter DNA methylation status of M1/M2 macrophage polarization markers STAT1, STAT6, MHC2, IL12b, iNOS, JAK1, JAK2 and SOCS5 in peripheral blood mononuclear cells of CAD patients. A case-control study was performed with 25 CAD patients and 25 controls to investigate the gene-specific promoter DNA methylation status using MS-HRM analysis. Our data indicates that there was a clear-cut difference in the pattern of gene-specific promoter DNA methylation of above mentioned genes in CAD patients as compared to controls. A consistent hypomethylated pattern was observed for most of the samples including both CAD patients and controls, which was heterogeneous DNA methylation as evident by their melting profiles. A significant difference was observed between the mean percentage methylation of STAT1, IL12b, MHC2, iNOS, JAK1 and JAK2 in CAD patients and control subjects. Our data showed that MS-HRM assay is a rapid and inexpensive method for qualitatively investigation and identification of aberrant gene-specific promoter DNA methylation changes in CAD. Since, monocytes and macrophages play a significant role in atherosclerosis, we propose that epigenetic markers including gene-specific promoter DNA methylation based on monocyte/macrophage might aid as diagnostic markers or drug targets for clinical application. Therefore, skewing the M1/M2 balance towards a more preferable phenotype through DNA methylation-related interventions may offer novel possibilities for atherosclerotic disease management.
Yin Hua Zhang
Seoul National University, Republic of Korea
Title: S-Nitrosylation of transglutaminase 2 impairs fatty acid-stimulated contraction in hypertensive cardiomyocytes
Biography:
Abstract:
Transglutaminase 2 (TG2) is a calcium-dependent enzyme and in the cardiovascularsystem, TG2 has been reported to be involved in the development of cardiac hypertrophy, vessel remodeling, and age related vascular stiffness. Interestingly, TG2 is implicated in the regulation of muscle metabolism via modification of respiratory complexes and the ADP/ATP transporter in the mitochondria of myocardium. However, the role of TG2 in the heart during conditions of pressure overload in relation to fatty acid(FA) oxidation has not been investigated. Hence, we investigated the involvement of TG2 in cardiomyocytes contraction under FA supplementation. Using TG2 inhibitor and TG2-deficient mice, we demonstrated that FA-supplementation activated TG2 and increased ATP level and contractility of cardiac myocyte from normal heart. By contrast, in cardiac myocytes from angiotensin-II treated rats and mice, the effects of FA-supplementation on TG2 activity, ATP level and myocyte contraction were abolished. Furthermore, TG2 was inhibited by S-nitrosylation and its level increased in hypertensive myocytes. Treatment with inhibitor for neuronal nitric oxide synthase (nNOS) restored FA-induced increase of TG2 activity and myocyte contraction. Moreover, intracellular Ca2+ levels were increased by FA-supplementation in both normal and hypertensive myocytes, showing that S-nitrosylation of TG2 but not alteration of intracellular Ca2+ levels are responsible for contractile dysfunction. These results indicate that TG2 plays a critical role in the regulation of myocyte contractility by promoting FA metabolism and provide a novel target for preventing contractile dysfunction in heart with high work-load.