This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. LDL to oxidized LDL (OxLDL)that is rapidly taken up by macrophages leading to coronary artery diseae (CAD). Paraxonase (PON), a HDL-bound polymorphic anzyme lowers OxLDL level and thus prevents CAD. It is hypothesized that light drinking (13-40g/day)increases serum PON level and theryby lowers OxLDL by preventing its formationor by destroying it and thus has a cardioprotective effect, whereas heavy drinking (>80g/day)has the opposite side effects.
The specific aims are: 1. To determine the relative concentration and activiry of the PON in light and heavy drinkers. 2. To characterize the genetic polymorphism of PON gene and correlate with the extent of alcohol exposure. 3. To determine the concentration of plasm OxLDL and correlate with their PON activity and the incidence of CAD. 4. To determine the ability of HDL's from each group to convert the biologically active oxidized-LDL to biologically inactive form and corrlate with corresonding PON acitiviy. To determine whether anti-PON can inhibit the destruction of OxLDL by HDL's 5. To determine the ability of HDL's from each group to prvent the uptake of OxLDL by macrophages and correlate with the corresponding PON activity. To determin where Anti-PON can specifically block the protective effecgt of HDL's.
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