Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/10/1996
Publication Date: N/A
Citation: Interpretive Summary: Cholesterol in the blood is a major risk factor for early heart disease. Cholesterol is carried mainly in the bloodstream on a particle known as low density lipoprotein, or LDL. It is known that LDL varies in size, that is, it has both large and small particles. It has been reported that patients with heart disease have smaller LDL particles than control subjects. Our purpose was to examine why LDL particles vary in size. Major fat (or lipid) components of LDL are not only cholesterol but also phospholipid and triglyceride. What we found was that small particles have less cholesterol and phospholipid and more triglyceride than large ones. Also, the thickness of the protein coat on the particle was thinner for small particles than for large ones. We hypothesize that this alteration in the protein on the surface of the particle causes changes in the ability of this protein to interact with the receptor that is responsible for breaking LDL down in plasma.
Technical Abstract: To investigate causes of variability in low density lipoprotein (LDL) particle size, we assessed LDL composition in plasma from 66 subjects by gradient gel electrophoresis. Lipoprotein concentrations were analyzed, and specific proteins were assessed. Results showed decreased anhydrous molecular weight with size, along with decreased relative content for cholesteryl ester, free cholesterol, and phospolipid, and increased triglyceride and protein content. As LDL size decreased, the ratio of surface cholesterol to phospholipid and of surface-to-core lipids, the fraction of surface area covered by lipid, and core volume also decreased. Based on surface pressures of 30 mN/m, the area covered by surface lipid was calculated to range from 6.45 Angstroms**2 x 10**4 to 3.10 Angstroms**2 x 10**4. Computer modeling indicates that alterations in the tertiary structure of apoB-100 are required to account for surface changes. To accommodate coverage of increasing relative surface area associated with decreasing size, apoB thickness at the interface was calculated to decrease from ~25 Angstroms to ~16 Angstroms. Such conformational changes in apoB may alter exposed epitopes, possibly causing changes in LDL receptor binding affinity and resistance to oxidation.