Research Summary

Exploring the role of intracellularly formed sphingosine 1-phosphate (S1P) in mediating the anti-atherogenic effects of adiponectin on endothelial cells

                                                                                                   

Dr Archna Singh                                                                                                              Dr Ambuj Roy

Principal Supervisor                                                                                                        Co- Supervisor

Host Instituition                                                                                                               Host Instituition

All India Institute of Medical Sciences,                                                                           All India Institute of Medical Sciences,

New Delhi, India                                                                                                             New Delhi, India

 

Despite recent advances in diagnosis, interventional techniques and pharmacological treatments targeting several risk factors of cardiovascular disorders (CVD), cardiovascular mortality is one of the leading causes of death globally. The pathophysiology of atherosclerosis, which is the hallmark of cardiovascular disorders is not fully elucidated. Research focus of our lab is metabolic derangements associated with obesity and atherosclerosis.

Three major anti-atherogenic molecules in circulation are high density lipoprotein (HDL), adiponectin and sphingosine 1-phosphate (S1P). Modulation of these molecules individually has not provided clinically relevant anti-atherogenic effects, which shows that the interplay between these molecules may be important in their impact on the development of atherosclerosis. The research funded by India Alliance explores how adiponectin, HDL and S1P provides anti-atherogenic effects on endothelial cells by acting in a sequential manner. Understanding the interplay between these molecules could provide new targets for modulation in order to modify cardiovascular disease risk in susceptible individuals, especially in the setting of obesity.

Other ongoing researches in our lab explore the functional aspects of HDL as a better predictor for cardiovascular risk compared to the traditional quantitative approach and the modulation of insulin resistance and HDL quality by adipose tissue in the setting of obesity.

 

Figure Legend: The hypothetical pathway explored in the research. AdipoR1: Adiponectin receptor subtype 1, SK1: Sphingosine kinase 1, ABCA1: ATP binding cassette transporter A1, S1P: Sphingosine 1-phosphate, HDL: High density lipoprotein and S1PR1: Sphingosine 1-phosphate receptor subtype 1
Lab website: www.aiims.edu