Atherosclerosis, 64 (1987) 211-214 Elsevier Scientific Publishers Ireland, Ltd 211 ATH 03910 Atherogenesis Preventive action of trifluoperazine D. Kaul and R.S. Kukreja Molecular Biology Unit, Experimental Medicine Department, Postgraduate Institute of Medical Education and Research, Chandigarh (India) (Received 19 February, 1986) (Revised, received 13 October, 1986) (Accepted 13 October, 1986) Summary This preliminary note describes the preventive action of trifluoperazine against cholesterol-induced atherosclerosis in rabbits. Although this drug had no significant effect on the elevated levels of serum lipids induced by the atherogenic diet, it completely inhibited the initiation of atherosclerotic lesions in rabbits fed atherogenic diets. Based on these findings, we propose that calmodulin and protein kinase ‘C may play a key role in the development of the atherosclerotic process. Key words: Atherogenesis; Calmodulin; Cholesterol; Protein kinase ‘C’; Rabbit; Trifluoperazine Introduction Both clinical and experimental evidence suggest a primary role of cholesterol in the pathogenesis of atherosclerosis. On the basis of our detailed studies [l-6] on human atherosclerotic lesions as well as membrane-model systems, we have re- cently proposed [3,5,6] that the cholesterol mole- cule (when present in higher amounts within cellu- lar membranes) creates a phase separation of bi- layer- and micellar-domains within membranes of smooth muscle cells leading to the process of atherogenesis. This hypothesis was further strengthened by reported studies [7-91 which re- vealed that many pharmacologically unrelated membrane-active compounds, such as chloro- quine, 17&estradiol, chlorpromazine, chloro- pheniramine (which are known to inhibit transi- tion from bilayer- to micellar-domains within membranes) were found to suppress [lO,ll] the atherosclerotic lesions. Further, it is interesting to note that a number of antiprohferative and anti- inflammatory drugs (having different mechanisms of action on the atherosclerotic process, as in- dicated by their effect on the cellular, lipid and fibrous components of the lesion) have been shown [ll] to be capable of preventing the formation of atherosclerotic lesions without reducing serum lipid levels. Further, there exists a general recogni- Correspondence address: Dr. D. Kaul, Molecular Biology Unit, Department of Experimental Medicine, Postgraduate Institute for Medical Education and Research, Chandigarh 160012, India. 0021-9150/87/%03.50 0 1987 Elsevier Scientific Publishers Ireland, Ltd.