Enzymatic Modification of Plasma Low Density Lipoproteins in Rabbits: A Potential Treatment for Hypercholesterolemia

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 8; pp. 3476 - 3480
• Main Authors: Labeque, Regine, Claudy J. P. Mullon, Joao Paulo M. Ferreira, Lees, Robert S., Langer, Robert
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.04.1993; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Aorta - pathology; Arteriosclerosis - pathology; Arteriosclerosis - physiopathology; Bile; Bile - metabolism; Biological and medical sciences; Blood; Blood plasma; Bones, joints and connective tissue. Antiinflammatory agents; Cholesterol; Cholesterols; Extracorporeal Circulation; Humans; hypercholesterolemia; Hypercholesterolemia - blood; Hypercholesterolemia - metabolism; Hypercholesterolemia - therapy; Lipoproteins; Lipoproteins, LDL - blood; Lipoproteins, LDL - pharmacokinetics; Liver; Medical sciences; Metabolic Clearance Rate; Metabolism; modification; Pharmacology. Drug treatments; phospholipase A2; Phospholipases A - metabolism; Phospholipases A - therapeutic use; Phospholipases A2; Phospholipids; Phospholipids - analysis; Phospholipids - metabolism; plasma; Proteins; Rabbits; Radioactive decay; Tissue Distribution; treatment; Filtration; Enzyme; Rabbit; Phospholipid; Metabolic diseases; Hyperlipoproteinemia; Lagomorpha; Metabolism; Enzymopathy; Phospholipase A; Cholesterol; Cardiopulmonary bypass; Lipoprotein LDL; Vertebrata; Experimental disease; Mammalia; Hypercholesterolemia; Treatment; Immobilized enzyme
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.8.3476

Phospholipase A2(EC 3.1.1.4) hydrolyzes certain phospholipids of low density lipoprotein (LDL). Plasma clearance of phospholipase A2-modified human LDL is up to 17 times faster than that of native human LDL in hypercholesterolemic rabbits. Modification of blood lipoproteins of hypercholesterolemic rabbits was performed by using an extracorporeal circuit containing immobilized phospholipase A2. After 90-min treatments, nearly 30% decreases in plasma cholesterol concentrations were observed. Erythrocyte, leukocyte, and platelet counts showed no net change after treatment. This technique does not require any fluid replacement or sorbent regeneration and offers a potential approach for lowering serum cholesterol and LDL levels.