Symposium on Atherosclerosis

and Metabolism of the Arterial Wall RICHARD J. BING. MD. FACC. Guest Edifor

Introduction Lipid accumulation in the arterial wall is the final link in the chain of events leading to atherosclerosis. How lipids, including cholesterol and cholesterol esters, penetrate the arterial areas or how they are synthesized, is of major importance in the development of atherosclerosis. No biological event is ever a single unified process; rather, it contains finer, more subtle mechanisms that contribute to its complexity and paradoxically also to its simplicity. So it is in the field of atherosclerosis and metabolism of the arterial wall. Questions arise as to how lipid synthesis takes place in these structures, how cholesterol penetrates the arterial wall, what factors facilitate or impede its entry into the wall, whether or how cholesterol binds, precipitates or segregates and, finally, how it is again released into the plasma. There are many additional important questions that need to be answered. They deal with the various theories of atherogenesis in its relation to the arterial wall: Does material contained in the atherosclerotic plaque arise as a degenerative process, are lesions in the arterial wall derived from thrombi, does platelet stickiness represent the nidus of the atherogenic lesions, or does the arterial wall take up, by a process of filtration, the material which eventually results in the atherosclerotic plaque? Other more fundamental questions are closely concerned with the metabolic activity of the arterial wall. They concern lipid synthesis in subcellular structures and the incorporation of building stones of larger molecular weight into lipids. In few other fields of pathologic physiology are species differences of such overriding importance as in atherosclerosis. Most of the work has been done on arteries of animals that differ in their metabolic function from their human counterparts. The question of whether or not cholesterol synthesis does take place in human coronary arteries is of importance in the mechanisms of the disease. Another problem that modern surgical methods has brought to the foreground is the possibility of development of atherosclerosis in human veins exposed to arterial pressure after their implantation. The papers in this Symposium address themselves to these subjects. The papers by Walton and by Zilversmit review the subject from their individual vantage points. Thus, Walton proposes that atherosclerotic plaques arise because altered endothelial permeability allows certain reactive macromolecular plasma proteins to permeate the endothelium. He therefore adheres to the idea of insudation first proposed by Virchow. Zilversmit warns against the pitfalls inherent in the use of isotopically-labeled material. The problems to which he addresses himself are concerned with the methods of administration of la-

beled cholesterol and the calculation of uptake and release. He critically reviews the filtration theory of atherogenesis. He points out that notwithstanding the limitation of in vitro experiments for the measurement of cholesterol release, in vitro experiments offer greater possibilities for control of essential variables than those performed in intact animals or in man. Whereat and Rabinowitz are concerned with the rate and product of lipid synthesis from acetate-1-14C in mitochondria isolated from control and atherosclerotic rabbit aortas. They propose a hypothesis based on the assumption that cholesterol feeding alters transport functions of the mitochondrial membranes of aortic smooth muscle cells. Fundamental studies are also carried out by Stein and Stein, who work on smooth muscle cells derived from rat aortic media and grown in culture for as long as 60 days. They study active lipid synthesis with labeled precursors and present evidence that their preparation can become useful in the investigation of phospholipid turnover in cells derived from vascular structures. Finally, Sarma and his associates stress the importance of species differences and the advantage of in vitro preparations in the investigation of lipid synthesis and cholesterol transfer. They use, almost exclusively, coronary arteries obtained from man, obtained at autopsy and demonstrate that cholesterol is not synthesized in the coronary arterial wall. However, there is considerable uptake of cholesterol from the perfusion fluid. They examine further the influence of hypoxia, carbon monoxide and collagenase and hemodyanamic changes on lipid synthesis and transport in these human vessels. They found that 7-ketocholesterol inhibits cholesterol uptake by the coronary arterial wall, a discovery that may be significant from both theoretical and practical points of view. The facts emerging from this Symposium are that a study of the relation between structure and function of the arterial wall is essential. Species differences must also be carefully considered. As often in science, our results are limited by the techniques used. This Symposium stresses that each technique contributes its share and that the final picture will eventually emerge from a variety of views obtained from a variety of techniques, Richard J. Bing, MD, FACC Huntington Memorial Hospital Pasadena, California and University of Southern California Los Angeles, California

April 1975

The American Journal of CARDIOLOGY

Volume 35


Symposium on atherosclerosis and metabolism of the arterial wall. Introduction.

Symposium on Atherosclerosis and Metabolism of the Arterial Wall RICHARD J. BING. MD. FACC. Guest Edifor Introduction Lipid accumulation in the arte...
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