Award Presentations

P-01/CO-01 : Gene polymorphism in essential hypertension & its relation to environmental factors in North Indians

posted Jan 26, 2017, 8:43 AM by sourav ghosh

Qulsoom Naz, Narsingh Verma, M. Serajuddin, A.A.Mahdi, M.L.Patel 
King George's Medical University, Lucknow, India

Aim- We aimed to determine genotype and allele frequencies of angiotensinogen (AGT) and alpha adducing (ADD1) polymorphisms in patients with essential hypertension.
Methods- We recruited total 205 subjects. In which 105 were essential hypertensive and 100 were Healthy controls. DNA samples for each individual were isolated from peripheral blood by standard phenol /chloroform method analyzed by polymerase chain reaction & enzymatic digestion. Lipid profile was analyzed by VITROS ̊ 250 Dry Biochemistry Fully auto-analyzer (Gonson & Gonson Company). Electrolytes (in serum & urine) were measured by ion-selective electrodes (Roche Hitachi MODULAR, Hitachi Ltd) in Clinical lab of Biochemistry.
Results- The distribution for each ADD1 genotypes were 61.96% for GG (69), 33.51% for GT (21) and 4.53% for TT(11) in the essential hypertensive group; 82.72% for GG (91), 16.46% for GT (9) and 0.82% for TT in the control group. The distribution of AGT genotypes was found significantly different between groups (x2 = 10.00: df = 2; P = 0. 006).
The frequencies for each of the AGT genotypes were found as 44.66% for MM (43), 44.33% for GT (49), and 11% for TT (9) in essential hypertensive group; 64% for MM (66), 32% for GT (36), and 4% for TT (3) in healthy control group. The distribution of AGT genotypes did not highly significant as compared to AGT between the groups. We suggest that AGT and ADD1 gene polymorphism play a role for development of essential hypertension (x2 = 9.767: df = 2; P = 0.007). 
Conclusion- Patients with essential hypertension exhibited higher levels of Serum cholesterol, LDL Cholesterol & TG than in control subjects. Taken together the genotype and biochemical parameters & considering the restrictive selection criteria used, the present results suggest a relationship between these gene polymorphism and essential hypertension in North Indians.

P-02/CO-02 : Endothelial Nitric Oxide Synthase (eNOS) gene expression of Endothelial Progenitor Cell (EPC) in Premature Coronary Artery Disease (PCAD) patients in Indian Population: A determinant of circulatory

posted Jan 26, 2017, 8:41 AM by sourav ghosh

Atanu Sen1Kranthi Vemparala1Ambuj Roy2Vinay Kumar Bahl2Dorairaj Prabhakaran3, Neera Nath4Subrata Sinha5Pradipta Nandi2Ravindra Mohan Pandey6Kolli Srinath Reddy7Ajay Manhapra8Ramakrishnan Lakshmy1
(1) Department of Cardiac Biochemistry, All India Institute of Medical Sciences, New Delhi, India, (2) Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India, (3) Centre for Chronic Disease Control and CARRS COE, Public Health Foundation of India, New Delhi, India, (4) Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India, (5) National Brain Research Centre, Manesar, Haryana, India, (6) Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India, (7) Public Health Foundation of India, New Delhi, India, (8) Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA


Introduction: A significant number of Ex-vivo and animal studies has already established that the reduced eNOS gene expression in EPC may leads to impaired mobilization of cells from bone marrow and that in turn results a reduced number of circulatory EPC in CAD patients. However in vivo eNOS gene expression of EPC from PCAD patients is yet to be known. Since in developing countries like India, the occurrence of cardiovascular disease at young age is markedly increasing, our present study aimed to investigate in vivo eNOS gene expression of EPC in PCAD patients and age matched healthy controls.
Method: Endothelial progenitor cells were isolated from peripheral blood on the basis of cell surface antigens CD34+/KDR+ by Magnetic Activated Cell sorting (MACS) method from 50 PCAD patients and 50 healthy controls. The intracellular eNOS gene expression was assessed by RT PCR method by using constitutive gene GAPDH as a reference gene. 
Result: A reduced eNOS gene expression (mean eNOS/GAPDH integrated density ratio)in EPC from PCAD patients compared to healthy controls were found (0.998±0.096/1.063±0.107) with a p-value of 0.002 and this difference was persisted even after adjustment for confounding factors like age, sex, BMI, smoking and statin therapy (p=0.002).
Conclusion: Our previous study had shown a significantly reduced number of CD34+/KDR+ cells in PCAD patients in comparison with healthy controls (.01868 ± .0176975/ .039972 ± .0299683; p<0.0001), which when supported by the result of the present study may delineate a possible cause of reduced circulatory level of EPC. Also as the study determined the eNOS gene expression directly in EPC isolated from study subjects, the result more realistically reflect the in vivo condition.

P-23/CO-03 : Impact of Gene Polymorphisms, Platelet Reactivity, and the SYNTAX Score on 1-Year Clinical Outcomes in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

posted Jan 26, 2017, 8:36 AM by sourav ghosh   [ updated Jan 26, 2017, 8:36 AM ]

Rama kumari
Nizam's Institute of Medical Sciences, Hyderabad, India

Background: High on-treatment platelet reactivity (HPR) has emerged as risk factor for stent thrombosis and major adverse cardiovascular events (MACE) in patients who receive Clopidogrel after percutaneous coronary intervention (PCI). the SYNTAX score (SS) has been shown to be associated with an increased risk of mortality, myocardial infarction MI, and the stent thrombosis in patients with ST-segment elevation acute coronary syndromes (ACS) undergoing PCI. We studied 1) the association between platelet reactivity and the SS for the risk of MACE in patients with ACS undergoing PCI treated with Clopidogrel; 2) the association between genetic variants involved in Clopidogrel-mediated platelet effects and the risk of MACE; 3) the incremental prognostic value of the platelet reactivity measured at several time points Methods Eighty four in-patients with ACS were enrolled .HPR was determined before PCI, at hospital discharge, and at1 month. The risk of MACE (cardiac mortality, MI, and stent thrombosis) with 1-month HPR and the SS in the period between 1 month and 1 year was investigated. The determination of platelet aggregation was done by using a platelet aggregometer > 46 AU and <19 AU HPR and LPR in the setting of PCI have been defined by the (ROC) curve analyses. Genetic analysis of CYP2C19 was done by PCR-RFLP technique.
Results: The relative impact of HPR, SS and genetic variants modulating Clopidogrel effects and the risk of MACE in patients with ACS undergoing PCI was studied. CYP2C19*2 was associated with HPR but was not independently associated with the risk of MACE at any point. Patients with HPR and a high SS displayed a higher risk of MACE compared with patients with HPR and a low SS. By cox regression analysis for MACE, it was found that there was 3 fold more hazard of developing MACE though statistically not significant with increase in platelet reactivity at 1 month. 
Conclusion: HPR is associated with increased rates of ischemic events in patients with high SS suggesting a possibility that platelet function testing could be implemented to optimise antiplatelet therapy.

P-26/CO-04 : A randomized controlled trial to assess the effectiveness of nurse based heart failure management programme

posted Jan 26, 2017, 8:33 AM by sourav ghosh   [ updated Jan 26, 2017, 8:34 AM ]

Mamata RaiKamlesh K. SharmaSandeep SethPragya Pathak
All India Institute of Medical Science, New Delhi, India

Aim: To assess the effectiveness of nurse based heart failure management programme. 
Methods: The study was conducted from June 2016 to December 2016 in the Cardio-Neuro-Centre, OPD, AIIMS, New Delhi in 50 HF outpatients (25 experimental and 25 controls) with mean age 39.52±15.7 years NYHA class –I, II & III with 3 months follow-up.
Nurse based HFMP is a set of activities which includes formal health teaching, Hriday card (which includes demographic profile, medicine chart, B.P & weight monitoring log, self-management plan and control measures), telemonitoring through a mobile application named Dhadkan app (it is telemonitoring system in android mobile, which helps to transfer subject’s vital parameter record i.e. B.P, weight, heart rate) and phone call once a week.
Outcome measures were QOL, drug adherence, re-admission and mortality rate.
Results: The results showed QOL score among experimental group was (60.00±17.51), (66.66±12.26) at pre and post respectively whereas in Control group it was (51.66±17.0) (53.33± 16.13) as measured by kansas city cardiomyopathy questionnaire (KCCQ) .The drug adherence score was (17.48±2.32) (15.24 ±1.36) at pre and post in experimental and (17.68 ±2.23) (16.72 ± 1.76) in control group as measured by adherence to refills and medications scale (ARMS) after 3 months of intervention. No re-hospitalization and mortality were reported in any of the study groups.
Conclusion: Nurse based HFMP was found to better in terms of improving QOL and drug adherence in the experimental group as compared to control group.
Key Words: Heart failure, Nurse based Heart Failure management programme, Quality of life, drug adherence, re-admission and mortality rate.

P-39/ CO-05 : Two different spectrums of Arrhythmogenic cardiomyopathy

posted Jan 26, 2017, 8:30 AM by sourav ghosh

Deepak Tewari1Hermohander S Isser2Praloy Chakraborty2Sudheer Arava3
(1) V.V.V. College for Women, Virudhunagar, India (2) Vardhman Mahavir Medical College (VMMC) and Safdarjang Hospital, New Delhi, India (3) All India Institute of Medical Science New Delhi, India


Background: Although classically known as ARVC/ARVD, Arrhythmogenic cardiomyopathy can affect both ventricles, RV only and rarely LV only. We present two cases of different spectrum, one of the common types (biventricular type) and another rare type (Left dominant type).
Patients and Methods: 
Case 1: 64 years female patient presented with VT of RV origin. Echocardiography documented LVEF=50%. Coronary angiography was normal. Contrast enhanced cardiac MRI showed mild biventricular dysfunction and late gadolinium enhancement (LGE) distributed in both ventricles. Endomyocardial Biopsy(EMB) shoed fibro fatty changes and myocyte loss.
Case 2: 45 years male presented with VT from LV. Echocardiography and coronary angiography was normal. CMRI showed normal biventricular function with patchy LGE involving LV and IVS. EMB from IVS showed shoed fibro fatty changes and myocyte loss. A diagnosis of left dominant Arrhythmogenic cardiomyopathy (LDAC) was made. The individual showed a variation in TMEM 43 gene (p.Thr277Ser).
Discussion: Arrhythmogenic cardiomyopathy is a rare form of inherited cardiomyopathy characterized by fibro fatty replacement and myocyte loss. It presents with ventricular arrhythmias with or without features of ventricular dysfunction. The commonest form involves the free wall of right ventricle and known as ARVC/D however in later stage in affects the LV also. Isolated involvement of LV is rare and occurs in less than 5% cases. The disease is caused by mutation in desmosomal genes. TMEM 43 is is a highly conserved inner nuclear membrane (INM) protein. It has been hypothesized that mutant TMEM43 protein would disrupt structure and function of desmocollin-2, desmoglein-2, desmoplakin, and junctional plakoglobin, leading to Arrhythmogenic cardiomyopathy.

P-38/CO-06 : Pleomorphic manifestations of sodium Channelopathy In a family

posted Jan 26, 2017, 8:27 AM by sourav ghosh

Soumya R Mahapatra1Praloy Chakraborty1, H S Isser1Sudheer Arava2, Kausik Mandal3
(1) Vardhman Mahavir Medical College (VMMC) and Safdarjang Hospital, New Delhi, India (2) All India Institute of Medical Science New Delhi, India, (3) Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow, India


Introduction: Cardiac Channelopathy affecting sodium channel mutation may have multiple clinical manifestations.
Results: A 50 year old female presented with sustained monomorphic ventricular tachycardia requiring DC cardioversion. Post cardioversion she developed bradycardia with irregular ventricular rate and no visible P wave. Echocardiography showed dilatation of right atrium (RA) and right ventricle (RV). Invasive electrophysiological testing showed presence atrial electrogram but despite highest output pacing, right atrium could not be captured. Son of the proband (30 year, male) presented with history of syncope. Surface ECG revealed absent P wave. Echocardiography showed dilatation of RA and RV. Invasive electrophysiological testing was suggestive of atrial standstill. A histological specimen from the right ventricular endocardium was normal. Sister of proband (38 year female) presented with intermittent atrial fibrillation and incomplete RBBB. 24 hours monitoring showed long sinus pauses. Echocardiography showed dilated RA and RV. Invasive electrophysiological testing showed electrically active right atrium. Son of the proband was subjected to genetic analysis by Next Generation sequencing (NGS) technique, which showed that the individual harbours variation in SCN5A (p.Asp1275Asn) and BRCA1 (p.Ser1503Ter) gene. Mutation analysis study showed that proband and her sister harbour the same variation in SCN5A and BRCA1.
Apart from LQTS3 and Brugada syndrome, SCN5A mutation can cause inherited progressive cardiac conduction defect (PCCD), sick sinus syndrome, atrial fibrillation, dilated cardiomyopathy and atrial standstill. Overlap syndromes of cardiac sodium Channelopathy consisting of multiple rhythm disturbances within one family, as in our case have also been reported. Concurrent role of BRCA1 mutation is not clear. BRCA1 mutation has been reported to be associated with increased cardiac apoptosis. Whether it is implicated with the disease manifestations (direct or as genetic modifier) or it is an incidental polymorphism, requires further research.
Conclusion: We report a family presenting with various arrhythmias associated with SCN5A and BRCA1.

P-03/ BO-01 : Post-transcriptional regulation of 3-hydroxy-3-methyl glutaryl-coenzyme A reductase: crucial role of the microRNA miR-27a

posted Jan 26, 2017, 6:40 AM by sourav ghosh

Abrar A. Khan, Vinayak Gupta, Kalyani Ananthamohan, Vikas Arige, Anil Kiran Chokkalla, Nitish R. Mahapatra
Department of Biotechnology, Bhupat and Jyoti Mehta School of Bioscience, Indian Institute of Technology Madras, Chennai , India

Dyslipidemia is a strong predictor of cardiovascular diseases including Essential Hypertension (EH). 3-Hydroxy-3-Methyl Glutaryl-Coenzyme A reductase (Hmgcr), coding for the rate-limiting enzyme in the cholesterol biosynthesis, is an important candidate gene for EH. However, the regulation of Hmgcr, especially at the post-transcriptional level, is incompletely understood. We set out to explore the possible roles of miRNAs in the regulation of Hmgcr. In silico predictions coupled with systematic functional analysis revealed specific interaction of miR-27a with mouse Hmgcr 3’-UTR in mouse liver fibroblasts AML-12. Furthermore, miR-27a showed a significant negative correlation with Hmgcr expression in cultured AML-12 cells as well as rat liver, kidney and skeletal muscle tissues. Ribonucleoprotein Immunoprecipitation (RIP) assays using antibodies against Ago2 in human hepatocellular HuH-7 cells over-expressing miR-27a revealed enrichment of HMGCR in the Ago2-IP fraction. Next, we quantified the expression of miR-27a and Hmgcr protein levels in liver tissues of genetically hypertensive blood pressure high (BPH) and genetically hypotensive blood pressure low (BPL) mice. Liver tissues from BPH showed elevated Hmgcr protein levels and diminished miR-27a levels as compared to BPL. Interestingly, cholesterol depletion in AML-12 cells resulted in down-regulation of endogenous miR-27a while augmenting the Hmgcr protein levels. In corroboration, exogenous cholesterol treatment diminished Hmgcr protein levels while enhancing the miR-27a levels. In addition, miR-27a expression and Egr1 protein levels were elevated in AML-12 cells under hypoxic conditions. Interestingly, computational analysis of the 1 kb promoter region of mmu-miR-27a revealed multiple putative Egr1 binding sites. Moreover, over-expression/down-regulation of Egr1 augmented/diminished the miR-27a promoter activity in both AML-12 and HuH-7 cells respectively. This study highlights the role of miR-27a in the post-transcriptional regulation of Hmgcr, thereby implicating its plausible role in cholesterol homeostasis and hypoxia-like pathological conditions.

P-13/BO-02 : SIRT6 inhibits cardiac fibrosis by repressing SMAD3 transcription factor

posted Jan 26, 2017, 6:37 AM by sourav ghosh   [ updated Jan 26, 2017, 8:24 AM ]

Jaseer Muhamed1Faiz Ahamed1Mahesh P. Gupta2Nagalingam R. Sundaresan1
(1) Indian Institute of Science, Bangalore India, (2) Cardiothoracic Surgery Research Program, Biological Sciences Division And The Pritzker School of Medicine, University of Chicago, Chicago

Objective: Cardiac fibrosis is a major complication associated with aging and several cardiovascular diseases. Till now, there is no definitive therapy available for treatment of cardiac fibrosis. Our previous study identified the class-III histone deacetylase SIRT6 as a key regulator of cardiomyocyte hypertrophy. Objective of this study is to understand the role of SIRT6 in cardiac fibrosis. 
Methods: Cardiac fibrosis and TGF-β1 signaling was evaluated by histology and western blotting in SIRT6 deficient mice hearts. Gene expression was studied by real time RT-PCR. Neonatal cardiac fibroblasts were used for in vitro genetic experiments. TGF-β/SMAD3 signaling and α-SMA promoter activity was evaluated by luciferase assays. SIRT6 and SMAD3 interaction was probed by co-immunoprecipitation. SMAD3 occupancy in TGF-β1 promoter was investigated by chromatin immunoprecipitation (ChIP) assay. 
Results: Histology and or immunoblot analysis of SIRT6-/- mice heart, and SIRT6-/- fibroblasts showed increased expression of fibrotic markers like fibronectin 1, collagen 1a, and alpha smooth muscle actin (SMA). Interestingly, TGF-β/SMAD3 signaling was found to be spontaneously activated in SIRT6-/- heart and fibroblasts, which is associated with transcriptional up-regulation of TGF-β/SMAD3 signaling genes. Moreover, SIRT6 deficient cells express increased membrane associated TGF-β1 under basal conditions. On the other hand, over expression of SIRT6 in cardiac fibroblasts decreased the expression of fibrotic markers and TGF-β/SMAD3 signaling. Immunoprecipitation and Chromatin immunoprecipitation results suggested that SIRT6 interact with SMAD3 transcription factor and reduces the occupancy of SMAD3 to TGF-β1 promoter resulting in the repression of TGF-β1 promoter. Finally, inhibition of SMAD3 with specific inhibitor rescued the fibrotic phenotype of SIRT6 deficient cardiac fibroblasts.


P-20/BO-03 : Dysregulated miR-25, -99, -155, -451 and Renin Angiotensin System in High salt diet – induced Cardiac dysfunction of uninephrectomized rats

posted Jan 26, 2017, 6:32 AM by sourav ghosh



Venkateswara Rao Amara, Sunil Kumar Surapaneni, Kulbhushan Tikoo
National Institute of Pharmaceutical Education and Research (NIPER) S.A.S. Nagar, Mohali, India

Background & rationale: Uninephrectomy is not associated with major adverse cardiovascular or renal events both preclinically and clinically. Due to modernisation, excursion in food habits such as increased intake of salt, fructose, sucrose, carbohydrates, fats, etc. is seen at alarming rate. The deleterious effects of high salt intake are well known in normal (binephric) condition, but that of in the live kidney donors is largely unknown. Hence, the present study was undertaken to get an insight into the development and progression of cardiac dysfunction in uninephrectomized rats fed with high salt diet.
Methods: Studies conducted so far started high salt diet immediately after uninephrectomy surgery, which is least likely to occur in clinical scenario. In order to exactly mimic the clinical situation, we fed the uninephrectomized rats initially with normal pellet diet for 12 weeks and then for 20 weeks with high salt diet (10% w/w NaCl). Kidney function tests (albumin, urea and creatinine), cardiovascular functions (SBP, DBP, HR, LVSP, LVEDP, +dP/dt, -dP/dt, baroreflex sensitivity) were measured at the end and histological, molecular studies (western blotting and RT-qPCR) were carried out after sacrifice.
Results: Uninephrectomized rats fed with high salt diet exhibited renal and cardiovascular dysfunction manifested in the form of decreased baroreflex sensitivity, increased in vivo cardiovascular reactivity to angiotensin II. Cardiac dysfunction is associated with decreased SERCA, AMPK and increased AKT and corresponding alteration in the miRNA (miR-25, -451, -99b, -155) regulating the expression of these proteins. The pattern of circulating miRNAs is opposite to that of the tissue miRs.
Conclusion: This study gives a preliminary idea on the cardiovascular and renal function of live kidney donors consuming high salt diet. Since the levels of tissue and circulating miRs do not match with each other, caution must be exercised in harnessing their role as diagnostic and prognostic markers.

P-27/ BO-04 : Risk Prediction of Acute Coronary Syndrome by Circulating sTLT1 level in Indian subpopulation

posted Jan 26, 2017, 6:28 AM by sourav ghosh   [ updated Jan 26, 2017, 6:34 AM ]

Apabrita Ayan DasTanima BanerjeeDr.Praksh Chandra MandalDr. Arun Bandyopadhyay
CSIR-Indian Institute of Chemical Biology, Kolkata, India

Soluble TREM like transcript 1(sTLT1) is reported to be associated with inflammation and major processes related to atherosclerosis. This study aimed to examine the expression of sTLT1 in normal and patient population as well as to evaluate its prognostic significance. Here, ELISA and Western blot analysis were performed to check expression of sTLT1 in study groups. The results showed that sTLT1 expression was significantly higher in ACS patients and asymptomatic population than control population (p<0.05).Moreover, correlation studies showed that sTLT1 level was not only associated with common ACS risk factors in both patient and asymptomatic group but also correlated with disease severity (LVEF, GRACE and TIMI score). Further correlation studies on sTLT1 level and total atherosclerotic burden (tunica intima-tunica media thickness) indicated a significant relation between these two variables pointing the potential of this protein as a risk predictor. ROC curve analysis for both the groups showed that sTLT1 had two definite cut off values for two separate study populations with better sensitivity and specificity. Lastly, logistic regression analysis against the risk factors showed it can act as an independent risk predictor in both patient and normal population respectively.

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