Investigations of novel subtypes of high-density lipoprotein in relation to cardiometabolic traits, lifestyle factors, and cardiovascular disease in three US-based cohorts

• Applicant: Dr. Manja Koch
• Subject Area: Epidemiology and Medical Biometry/Statistics ; Nutritional Sciences ; Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2015 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 283850885

Cardiovascular diseases (CVD) continue to be the leading causes of death worldwide. Ample evidence from observational studies indicates that high-density lipoprotein (HDL), as measured by either the concentration of cholesterol (HDL-C) or the concentration of apolipoprotein AI (apoAI, the main protein component of HDL) is inversely associated with the risk for CVD. However, whether HDL is causally related to CVD remains a matter of debate. HDL is increasingly recognized as a heterogeneous group of particles varying in protein composition, structure, and functional properties. Accordingly, new HDL research is focused on HDL functions, and the development of novel measures that capture such properties. Proteins that associate with HDL (the HDL proteome) have powerful impact on the downstream functional properties and metabolism of HDL by mediating interactions with enzymes and receptors. To better understand the functional importance of HDL-associated proteins, it is for instance possible to define subtypes of HDL based on the presence or absence of defined proteins. As an example, a recent study reported that only HDL that did not contain any apolipoprotein CIII (apoCIII) was inversely associated with risk of coronary heart disease (CHD), whereas HDL containing apoCIII was positively associated with CHD. Besides apoCIII, modern proteomic approaches have identified more than 85 proteins that are associated with HDL. Much is known about the role of the specific proteins in lipid metabolism, inflammation, and immunity. However, little is known about the relation of HDL subtypes containing or lacking these proteins to cardiometabolic traits and cardiovascular events. The research group of Prof. Jensen at the Department of Nutrition at the Harvard T.H. Chan School of Public Health focuses on the evaluation and measurement of new HDL subtypes with respect to their association with CVD. The aims of the proposed research project are twofold: 1. To investigate associations of HDL subtypes containing vs. lacking apoCIII with cardiometabolic traits, modifiable lifestyle factors and subclinical CVD traits in the Multi-Ethnic Study of Atherosclerosis. 2. To investigate associations of 20 novel HDL subtypes with the risk for incident CHD in the Nurses Health Study II and Health Professionals Follow-up Study. The proposed investigation of several new, functionally relevant, HDL subtypes with respect to their association with cardiometabolic risk factors and CVD shall foster the understanding of the role of HDL in the etiology of CVD, and might potentially identify novel treatment targets.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Dr. Majken Jensen, Ph.D.