sodium-dodecyl-sulfate and Arteriosclerosis

Functionally interactive proteases of the plasminogen/plasmin and the matrix metalloproteinase (MMP) system degrade and reorganize the extracellular matrix of the vessel wall in atherosclerosis. Here we investigated whether such proteases are able to confer atherogenic properties onto low density lipoprotein by nonoxidative modification.. Similar to the recently described enzymatically-modified low-density lipoprotein (E-LDL), native LDL exposed to plasmin or matrix MMP-2 or MMP-9 and cholesterylester-hydrolase (CEH) showed extensive deesterification, with ratios of free cholesterol to total cholesterol rising to 0.8 compared with 0.2 in native LDL. When the ratio exceeded 0.6, both plasmin/CEH-LDL and MMP/CEH-LDL fused into larger particles. In parallel, they gained C-reactive protein-dependent complement-activating capacity. E-LDL produced with any protease/CEH combination was efficiently taken up by human macrophages, whereby marked induction of MMP-2 expression by E-LDL was observed. These in vitro findings had their in vivo correlates: urokinase-type plasminogen activator, MMP-2, and MMP-9 were detectable in both early and advanced human atherosclerotic lesions in colocalization with E-LDL.. Plasmin and MMP-2/MMP-9 may not only be involved in remodeling of the extracellular matrix in progressing plaques, but they may also be involved in lipoprotein modification during genesis and progression of atherosclerotic lesions.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Arteriosclerosis; Blotting, Western; C-Reactive Protein; Cells, Cultured; Complement Activation; Complement Hemolytic Activity Assay; Electrophoresis, Polyacrylamide Gel; Fibrinolysin; Humans; Lipoproteins, LDL; Macrophages; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Monocytes; Sodium Dodecyl Sulfate; Sterol Esterase; Trypsin

Topics: Animals; Aorta; Apoptosis; Arteriosclerosis; Base Sequence; bcl-2-Associated X Protein; Cholesterol, Dietary; Diet, Atherogenic; Disease Models, Animal; DNA Primers; Electrophoresis, Polyacrylamide Gel; Gene Expression Regulation; Muscle, Smooth, Vascular; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sodium Dodecyl Sulfate

Abnormalities of collagenous peptides were detected among a group of 20 patients with abdominal aortic aneurysms, studied by high-performance liquid chromatography/NaDodSO4-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) analysis of the cyanogen bromide (CB) cleavage products of insoluble skin protein. Three abnormal patterns were identified as follows: (1) relative deficiency of a peptide with a relative molecular mass of approximately 58 kilodaltons (four patients); (2) relative decrease in the ratio of alpha-2 to alpha-1 (I) CB peptides (seven patients); and (3) decreased detection of all collagenous CB and pepsin cleavage products (one patient, who was also heterozygous for the Z allele of alpha 1-antitrypsin). The "minimal hypothesis" to explain these findings is that most of the observed abnormalities can be explained by collagenolysis in vitro, although a mutation in the primary structure of collagen has not been ruled out in all patients. Molecular heterogeneity appears to occur within the aneurysm phenotype, and the findings in the patient in group 3 allow identification of one possible risk factor in abdominal aortic aneurysmal disease that has a genomic assignment.

Topics: Amino Acids; Aorta, Abdominal; Aortic Aneurysm; Arteriosclerosis; Chromatography, High Pressure Liquid; Collagen; Cyanogen Bromide; Electrophoresis, Polyacrylamide Gel; Humans; Pepsin A; Peptides; Phenotype; Sodium Dodecyl Sulfate

1. Effects of various drugs on cholesterol-induced atherosclerosis in rabbits during the progression phase have been studied. The drugs tested are antimetabolites (mercaptopurine, hydroxyurea), surface active agents (sodiumdodecyl sulfate), inhibitor of adrenocoritcal steroid synthesis (o, p'-DDD), lysosome stablizers (chloroquine, acetylsalicylic acid) with antihistaminic (chlorpheniramine) and cholesterol binder (nystatin). 2. Mercaptopurine treatment showed marekd reduction in both atherosclerotic lesions and cholesterol concentrations of the serum and aorta. 3. Hydroxyurea reduced both the aortic cholesterol concentration and the lesions, but the serum cholesterol concentration remained high. 4. Sodiumdodecyl sulfate and o, o'-DDD showed slight inhibition of the development of atherosclerosis. 5. Pyridinocarbamate showed a slight beneficial effect on the prevention of atherosclerosis only when it was administered prior to the meal. 6. Nystatin, chloroquine and acetylsalicylic acid + chlorpheniramine showed little effect.

Topics: Animals; Arteriosclerosis; Aspirin; Chloroquine; Cholesterol, Dietary; Clomipramine; Hydroxyurea; Male; Mercaptopurine; Pharmacology; Pyridinolcarbamate; Rabbits; Sodium Dodecyl Sulfate