Goal 2: Reduce Human Disease

Translational and basic research on high triglycerides as an additional risk for cardiovascular disease.

Compelling Question (CQ)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Previous studies have focused on high cholesterol as a risk factor for cardiovascular disease (CVD). Recent epidemiologic and genetic studies with apoCIII mutation, for example, have identified significant contribution of high triglycerides (TGs) to the development of atherosclerotic CVD. In particular, the epidemics of obesity, even from young age, in the US and worldwide have caused significant increases in the prevalence of hypertriglyceridemia, which has become a serious health problem. However, how hypertriglyceridemia increases risk for atherosclerotic CVD remains largely unknown. Further translational and basic studies would be needed to examine how TG-rich lipoproteins and cholesterol-rich lipoproteins cooperate to increase the risk for CVD. Basic research would need to be conducted at integrative, cellular and molecular levels including examining how TGs are metabolized and how TG-rich lipoproteins, along with cholesterol-rich lipoproteins, cause atherosclerosis. These studies would guide clinical approach on TG- versus cholesterol-lowering therapy for prevention and treatment of atherosclerotic CVD.

Feasibility and challenges of addressing this CQ or CC

The challenges include combining large clinical studies and basic research. Clinical studies includes confirming high TGs as an independent risk for atherosclerotic CVD, developing novel TG-lowering therapy and examining whether these novel TG-lowering therapy, with apoCIII as a target for example, would be beneficial in prevention and treatment of CVD. It is also important to examine effects of novel TG-lowering therapy on adiposity, adipose tissue function and risk of diabetes. Basic science needs to elucidate how TGs are metabolized in vivo, causing hypertriglyceridemia, and how hypertriglyceridemia increases risk for atherosclerotic CVD, and identify novel pathways for these pathophysiological processes, which would provide novel strategies for development of new therapy for CVD. Collaborative approach with great financial support will make all these feasible.

Name of idea submitter and other team members who worked on this idea Huaizhu Wu, MD

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Idea No. 860