Research Projects

Cardiovascular disease is one of the leading cause of morbidity and mortality worldwide. The prevalence of cardiovascular disease is on the rise especially in South Asian population. The pathophysiology of atherosclerosis, which is the hallmark of these cardiovascular disease is not fully elucidated. There are various anti-atherogenic molecules in circulation like HDL, adiponectin and sphingosine 1-phosphate (S1P). But taken individually their anti-atherogenic effects fail to be significant showing that the interplay between these molecules needs to be explored in greater detail in order to better understand their role in atherosclerosis. Adiponectin, a hormone secreted by adipose tissue has various beneficial physiological effects. This includes insulin sensitising, anti-apoptotic and antiatherogenic effects. The anti-atherogenic effect exerted by adiponectin on endothelial cells has been shown to be mediated by caveolin mediated recruitment of ceramidase which converts intracellular ceramide to sphingosine. This sphingosine is converted to S1P by sphingosine kinase. The proposed study explores the role of S1P in mediating the antiatherogenic effects of adiponectin. S1P is a physiologically active lipid mediator with proven anti-atherogenic effects on endothelium. Intracellular S1P needs to move to the extracellular compartment or the outer leaflet of the plasma membrane to activate the S1P receptors. This efflux of S1P is mediated by ATP binding cassette transporter A1 (ABCA1). Through this study we would also like to explore the role of ABCA1 in regulating the S1P mediated effects of adiponectin. The efflux of S1P through ABCA1 is regulated by binding of HDL or Apo-A1 to ABCA1 giving an additional layer of complexity. This could also regulate the effects of adiponectin mediated through S1P. This aspect also will be explored through this study. Altogether this study will explore how adiponectin, HDL and S1P causes very similar anti-atherogenic effects on endothelial cells by acting in a sequential manner.