Day 1 :
University of Manitoba, Canada
Time : 10:35-11:05
Naranjan S Dhalla is a distinguished Professor at the University of Manitoba and is the Director of Cardiovascular Developments at the St. Boniface Hospital Albrechtsen Research Centre. He has been investigating the pathophysiology and pharmacology of heart disease and has published 794 full length papers. His research work has been cited more than 22,600 times with h-factor of 71. He has given 350 symposia talks at various national and international conferences in addition to 340 talks at different institutions. He has received more than 178 honours and awards, including six honorary doctorate degrees and four honorary professorships from institutions all over the world.
Hypertension has been shown to be associated with an elevated level of intracellular Ca2+, which is determined by the functional status of both L-type Ca2+ channels and store-operated Ca2+channels in the vascular smooth muscle. Although L-type Ca2+ antagonists such as verapamil are known to exert anti-hypertensive actions, the effects of store-operated blockers such as SKF-36365 (SK) on blood pressure and cell proliferation have not been examined. In this study, SK was observed to reduce systolic and diastolic blood pressures in rats in a dose and time dependent manner. While SK showed no effect on basal [Ca2+]i in rat aortic smooth muscle cells, the increase in [Ca2+]i due to lysophosphatidic acid (LPA) or angiotensin II was depressed by this agent. On the other hand, norepinephrine- or the endothelin-induced increase in [Ca2+]i was not affected by SK. The cell proliferation, as determined by cell number as well as thymidine incorporation in the absence or presence of LPA, was reduced by SK. This agent was also observed to augment the verapamil-induced reduction in diastolic blood pressure without any effect on the verapamil-induced reduction in systolic blood pressure. In addition, verapamil was found to depress LPA-induced or ATP-induced increase in [Ca2+]I, these actions of verapamil were promoted by SK. The results suggest that store-operated Ca2+ channel blockers, which affect sites different from those for L-type Ca2+ channel antagonists, either alone or in combination, may be useful for the treatment of hypertension.
University of Montreal, Canada
Keynote: Geo-ethnic diversity, hypertension and renal impairment in diabetes: Therapeutic consequences
Time : 11:20-12:00
Pavel Hamet is the holder of the Canada Research Chair in Predictive Genomics. He is Professor of Medicine at Université de Montréal, Adjunct Professor of Experimental Medicine at McGill University, and Visiting Professor at the First Faculty of Medicine at Charles University, Prague, Czech Republic. He is currently chief of Gene Medicine Services, member of the Endocrinology Service, and Director of the Ecogenomic platform for complex diseases at the CHUM. He is also CEO and Chief Scientific Officer of Medpharmgene. Author or co-author of over 600 scientific publications, Dr. Hamet has received many honours, including the prestigious Wilder Penfield Award in 2001, was named Officer of the Ordre national du Québec in 2008 and received the Okamoto Award by the Japan Vascular Disease Research Foundation
Complications of type 2 diabetes (T2D) have been reported to be different between Asian and Caucasian populations with higher prevalence and severity of renal disease and stroke in Chinese, contrasting with lower myocardial infarction, that could not be fully explained by differences in hypertension prevalence or treatment. Our objective was to determine whether ethnic heterogeneity exists within the Caucasian population with respect to phenotypic and genomic determinants of vascular complications of T2D. We analyzed the two main features of renal impairment: increase of albuminuria as uACR and decline of estimated glomerular filtration rate as eGFR in Caucasian T2D patients followed during the 5 year period of the ADVANCE trial. Genetic ethnic origins of 5000 genotyped subjects were determined by principal component analysis with Eigenstrat software. The first principal component separated T2D individuals into two ethnic groups of Slavo-Baltic and Germano-Celtic origins. Phenotypic analyses and Genome Wide Association Studies (GWAS) for age of onset of T2D and changes in uACR and eGFR over the course of the study were performed in the two ethnic groups combined and separately. Patients of Slavo-Baltic origin had T2D at a significantly younger age and were more hypertensive in spite of higher number of antihypertensive drugs received. Baseline uACR was higher in individuals with a Slavo-Baltic genetic profile. The decline in eGFRCKD-EPI during the ADVANCE study was steeper among individuals with Germano-Celtic than with Slavo-Baltic genetic profile. Macrovascular events at baseline (myocardial infarction and stroke) were significantly higher in Slavo-Baltic subjects (p=1.3x10-2 and p=4.0x10-5) as was cardiovascular death (p=1.6x10-4) during the study. These characteristics persisted in Slavo-Baltic subjects living in Germano-Celtic environment suggesting a strong genetic contribution. A set of independent genetic variants (SNPs) were identified as markers of genes associated with early onset of T2D. They were used in a genetic risk score to predict age of death and response to therapy. Our studies revealed distinct genetic architectures of age of onset of T2D between two geo-ethnic groups within the Caucasian population that likely have clinical relevance.