title: Atherosclerosis, cell motility, calcium, and calcium-channel blockers.
abstract: Three key players in the humoral-cellular interactions that occur during the early development of atherosclerosis are presented as they activate platelets and vascular smooth muscle cells but eventually can be corrected by calcium-channel blockers. Platelet-activating factors via phospholipase C and phosphoinositides increase cytosolic calcium and phosphorylate contractile proteins, thereby inducing a change--aggregation and the secretory response of platelets. Low-density lipoprotein (LDL) has a similar hormone-like action and activates the signal transfer cascade that eventually leads to platelet aggregation as well as vascular smooth muscle cell proliferation. These effects can be greatly reduced by high-density lipoproteins. Platelet-derived growth factor stimulates the transcription of the LDL-receptor gene as well as the HMG-CoA reductase gene. The latter is inhibited by calcium-channel antagonists while the former is further enhanced. Thus, calcium-channel antagonists interfere with the stimulus-response coupling not only via slow calcium-channel influx inhibition but also by an additional membrane action and interference with gene activation.
authors.affiliation: Department of Research, University Hospitals, Basel, Switzerland.
authors.forename: L H
authors.initials: LH
authors.lastname: Block
authors.forename: F R
authors.initials: FR
authors.lastname: Bühler
mesh_terms: D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000502:physiology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D008077:Lipoproteins, LDL; D010972:Platelet Activating Factor; D010982:Platelet-Derived Growth Factor; D002118:Calcium