Agents to modulate high-density lipoproteins

There is great interest in developing new modes of therapy for atherosclerosis, particularly involving the modulation of high-density lipoproteins (HDLs), to treat coronary heart disease and stroke. Our lab is engaged in the design, synthesis, and characterization of peptides aimed at functionally mimicking apolipoprotein A-I (apoA-I), the predominant protein component of high-density lipoproteins (HDL).  A sizable body of evidence has established that HDL is protective against cardiovascular disease. HDL particles exist in constant dynamic flux. These nanoparticles vary in diameter from 5–13 nm, undergoing “remodeling” by virtue of proteins that mediate the influx, efflux, or modification of lipids and cholesterol within the particles. We are employing chemical, biophysical, biological, and proteomic approaches to gain an understanding at the molecular level of the network dynamics involved in HDL biogenesis and function.