Ca++-Antagonist Lanthanum POSSIBLE ROLE OF CALCIUM IN ATHEROGENESIS

out in this study, although no direct effects of La3+ on tissue metabolism have as yet been reported. This work was presented in part at the 31st Annual Meeting of the Council on Arteriosclerosis of the American Heart Association, Miami Beach, Fla., November 1977. Circulation. 56(Suppl. III): 145. Receivedfor publication 26 March 1979 and in revisedform 6 December 1979. INTRODUCTION As recently summarized by Ross and Glomset (1) the main processes leading to the formation of atherosclerosis plaques appear to be: (a) increased permeability ofarterial endothelium to macromolecules such as lipoproteins; (b) migration of smooth muscle cells (SMCs)l from the media into the intima; (c) proliferation ofthese cells by mitosis; (d) secretion by the increased SMCs ofexcessive amounts ofcollagen, elastin, and glycosaminoglycans; as well as (e) endocytosis (phagocytosis) of lipids and/or lipoproteins by intimal cells. Calcium mineralization, especially of arterial elastin, also appears to be a frequent integral part ofatherogenesis (2). Previous studies in rabbits (3-7) and pilot studies2 in monkeys (5, 6) have indicated that most of these atherosclerotic processes can be inhibited or completely suppressed by agents which prevent excessive deposition of calcium into arteries. These agents included ethane-l-hydroxy-1,1-diphosphonate, 3-amino1-hydroxy-propane-1,l-diphosphonate, azacycloheptane-2,2-diphosphonate as well as 2-thiophenecarboxylic acid and its methylated or bromated derivatives. These compounds exerted their antiatherosclerotic effect despite unmitigated high serum cholesterol levels when given in large enough amounts. Similar protective actions ofdiphosphonic acids also have been reported by others (8-11) in animal models of atheroarteriosclerosis. In addition, other drugs that inhibit arterial deposition of calcium or its use also have been shown to be antiatherogenic. These drugs include Mg-EDTA (12), pyridinol carbamate (13), chondroitin sulfate A (14), reserpine, guanethedine, propanolol (15, 16) (thyro)calcitonin (17), sodium p-hexadecylaminobenzoate (18, 19) and, as discussed by Numano et al. (20) and Numano (21), manganese, 'Abbreviation used in this paper: SMCs, smooth muscle cells. 2 Report on the completed study is in preparation. 967 J. Clin. Invest. X) The American Society for Clinical Investigation, Inc. 0021-9738/80/05/0967/15 $1.00 Volume 65 May 1980 967-981 Downloaded from http://www.jci.org on June 25, 2017. https://doi.org/10.1172/JCI109783