The Association of SAA With Apolipoprotein B Affects Cardiovascular Risk

Cardiovascular disease (CVD) is the leading cause of death in developed nations and a major health issue in Veterans. Despite a number of different treatments, cardiovascular disease remains a major health burden, thus further treatments are needed. Individuals with obesity and/or diabetes are at particularly high risk for cardiovascular disease, and research suggests that elevated levels of serum amyloid A (SAA) may contribute to cardiovascular disease, particularly atherosclerosis. In preliminary studies in both mouse and human the investigators have identified that SAA appears to shift between lipid particles. SAA is mainly found on high density lipoprotein (HDL) particles; however, the investigators have found that in both mice and humans with obesity and/or diabetes SAA is found on low density lipoprotein (LDL) and very low density lipoprotein (VLDL) particles, and the investigators hypothesize that the presence of SAA on LDL or VLDL makes these particles more likely to cause cardiovascular disease. To determine what leads SAA to shift between lipid particles, SAA knockout mice will be injected with HDL containing SAA then blood collected at several time points over 24 hours, and the lipid particles will be isolated to measure SAA. In some experiments the investigators will compare different isoforms of SAA, different types of HDL particles, or induce expression of enzymes likely involved in shifting SAA between particles. To determine if the presence of SAA makes lipid particles bind vascular matrix more strongly, the investigators will collect carotid arteries and compare the extent of lipid particles bound to the vascular matrix in the vessel wall when the particles have or do not have SAA present. If this research confirms this hypothesis then the presence of SAA on LDL or VLDL may 1) be a new marker indicating humans at highest risk for cardiovascular disease and 2) be a new target of therapy to prevent cardiovascular disease.