[The effect of Ca++ antagonists on cellular lipid metabolism].
The antiatherogenic effects of Ca2(+)-antagonists have been proved in animal studies and in man. It is suggested that drugs of this class--unlike lipid-lowering drugs--do not exert their effects by decreasing lipoprotein plasma levels but by a modulation of signal transducers. Ca2(+)-antagonists inhibit the extracellular matrix synthesis and thereby decrease cell adhesion and the modification of matrix-bound low density lipoproteins (LDL). Thus less modified LDL are produced, which are catabolized by scavenging or by phagocytosis of macrophages, leading to a reduction of foam cell production. Ca2(+)-antagonists also enhance the synthesis of membrane phospholipids, e.g. sphingomyelin (SPM), thereby increasing the membrane turnover and fluidity. In addition they positively influence the formation and catabolism of radicals. The resulting membrane protective effects possibly delay the general ageing process and improve the integrity of the cytoskeleton as well as of the adjacent membranes. In various studies it has been established that the use of Ca2(+)-antagonists leads to a reversal of atherosclerotic processes at the stage of early lesions. The effects of this class of drugs on a molecular level will be a focal point of future research. Of special importance will be the study of the cell specific signal transducing processes in those types of cells involved in atherosclerosis and the understanding of their role in the process as a whole.
Institu für Klinische Chemie und Laboratoriumsmedizin der Westfälischen Wilhelms-Universität, Münster/Westf.
G
G
Schmitz
J
J
Hankowitz
B
B
Brennhausen
C
C
Schmutte
D001161:Arteriosclerosis / Q000378:metabolism / Q000517:prevention & control; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism
D002121:Calcium Channel Blockers; D002784:Cholesterol
Der Einfluss von Ca+(+)-Antagonisten auf den zellulären Lipidstoffwechsel.