MONOCLONAL ANTIBODIES TO APOLIPOPROTEIN A-1

LIPOPROTEINS ARE HIGH MOLECULAR WEIGHT WATER-SOLUBLE COMPLEXES COMPOSED OF LIPID AND ONE OR MORE SPECIFIC PROTEINS. THEY ARE GROUPED ACCORDING TO THEIR DENSITY AS DETERMINED BY ULTRACENTRIFUGATION. PLASMA LOW DENSITY LIPOPROTEINS (LDL) CONTAIN APPROXIMATELY 75% LIPID AND 25% PROTEIN AND FUNCTION AS A MAJOR CARRIER OF CHOLESTEROL. APOLIPOPROTEIN B IS THE STRUCTURAL PROTEIN MOIETY OF LDL (1). THE MEASUREMENT OF ELEVATED LEVELS OF APOLIPOPROTEIN B HAS BEEN REPORTED TO BE A MARKER OF CORONARY ARTERY DISEASE (2). IN ADDITION THE MEASUREMENT OF REDUCED LEVELS OF HIGH-DENSITY LIPOPROTEIN (HDL) CHOLESTEROL (3) AND APOLIPOPROTEIN A-1 HAVE ALSO BEEN REPORTED TO BE A MARKER. HDL CONTAINS APPROXIMATELY 50% APOLIPOPROTEIN WITH 32% OF THE LIPID COMPONENT BEING CHOLESTEROL AND 65% OF THE APOLIPOPROTEIN BEING A-1(5). WE HAVE PREVIOUSLY DEVELOPED MONOCLONAL ANTIBODIES WITH SPECIFICITY FOR APOLIPOPROTEIN B FROM HUMAN PLASMA LDL (6). BECAUSE OF THE ROLE THAT LIPOPROTEINS PLAY IN THE PATHOGENESIS OF ATHEROSCLEROSIS THEIR QUANTITATION IS IMPORTANT NOT ONLY FOR METABOLIC STUDIES BUT FOR THE CHARACTERIZATION OF DYSLIPOPROTEINEMIAS. THE SPECIFIC AIMS OF THIS PROJECT ARE TO DEVELOP AND CHARACTERIZE MONOCLONAL ANTIBODIES TO HUMAN APOLIPOPROTEIN A-1 (PHASE 1) AND TO USE THESE ANTIBODIES AS REFERENCE STANDARDS FOR THE ISOLATION OR IDENTIFICATION OF APOLIPOPROTEIN A-1 AND AS SENSITIVE INDICATORS OF CORONARY ARTERY DISEASE (PHASE II).