What are Cardiovascular Diseases?
Why should these be studied?
What are cardiovascular diseases and why should we give emphasis to these diseases? Cardiovascular diseases (viz., coronary heart disease, heart failure, stroke etc.) affect a large section of the young and adult population and are the leading causes of morbidity/mortality worldwide. Recent studies have documented that although the mortalities associated with cardiovascular diseases are declining in high-income group countries such as Western Europe and North America, the burden of cardiovascular diseases continues to rise in the middle-income and low-income group countries including India. Notably, South Asians have a greater prevalence of cardiovascular risk factors than the rest of the world, and India itself is estimated to have more than half of the world’s heart disease patients at present. These diseases not only cause enormous loss of human lives, but also lead to huge health care costs, tremendous socio-economic burden, declining national productivity and quality of life. The determinants of cardiovascular diseases are multifactorial, complex and often interrelated. Stress, inadequate physical activity, smoking, higher intake of fats and sodium, lower consumption of potassium, fruits and vegetables are well-known risk factors for cardiovascular diseases. Besides these, a strong influence of genes in cardiovascular complications has also been established. Hypertension (elevated arterial blood pressure), dysregulated catecholamine homeostasis, dyslipidemia, increased oxidative stress, cardiac remodeling, protein misfolding are some of the chief risk factors for cardiovascular diseases. However, the pathogenesis of cardiovascular diseases remains incompletely understood.
We, at the Cardiovascular Genetics Lab, are interested in unravelling the genetic and molecular bases that underlie cardiovascular diseases with an aim for their early diagnosis, prognosis, management and treatment. In this direction, to elucidate how alterations in key genes/molecular factors contribute to disease phenotype, we study human subjects (cases versus controls), utilize rodent models (of hypertension, atherosclerosis and diabetes) as well as perform investigations at the cellular level (employing cultured cell lines). Moreover, we use multidisciplinary approaches to delineate the molecular interactions and signaling pathways that are disrupted in these pathological conditions. We are currently focusing on three broad aspects of cardiovascular complications which will facilitate identification of biomarkers and potential therapeutic agents as outlined below.
What do we do in CVG lab?
Discovery of functional genetic variations in Indian populations and their associations with cardiovascular diseases
We have discovered a number of genetic variants in the chromogranin A gene promoter and exonic regions (that translate to bioactive peptides such as anti-hypertensive/cardioprotective catestatin and dysglycemic pancreastatin) using case-control approach in Indian populations. Chromogranin A expression is dysregulated in several cardiovascular diseases. Linkage disequilibrium analysis and genetic association studies identified several genetic variations in chromogranin A locus that enhance the risk for cardiovascular/metabolic disorders in the Indian population. Furthermore, using various experimental (cellular/biochemical/biophysical/physiological assays), and computational (molecular modelling, molecular dynamic simulations, docking of peptides with their receptors) we demonstrated that these variants alter the expression of chromogranin A or potency of catestatin /pancreastatin peptides. Similarly, we have recently identified functional variants in the regulatory region of matrix metalloproteinases and established that these variants alter the risk factor for cardiometabolic disorders. Results from these studies provide new insights into the molecular mechanisms contributing to cardiovascular diseases. These studies have implications for development of diagnostic and therapeutic strategies for management of the cardiovascular diseases.