In Vitro Studies of Phospholipid Synthesis in Experimental Atherosclerosis

Abstract

Using in vitro techniques and labeled linoleic acid and glucose, alterations in phospholipid synthesis in the aorta were correlated with electron microscopic studies at various intervals of time after feeding rabbits cholesterol. After 4 to 8 weeks of feeding, more phospholipid precursors were incorporated into die phospholipids of atherosclerotic blood vessels than of normal vessels. Concomitant with the metabolic alterations, the following ultrastructural changes occur. Smooth muscle cells of the plaque (myo-intimal cells) evolve into highly vacuolated cells containing a profusion of cytoplasmic organelles. The increase in membranous organelles suggests that the increase in phospholipid synthesis may be the result of a cellular requirement for increased intracytoplasmic structural phospholipid. ADDITIONAL KEY WORDSatherosclerotic plaque smooth muscle cells phospholipid metabolism experimental atherosclerosis glucose metabolism intracellular organelles phospholipid synthesis electron microscopy linoleic acid blood vessel metabolism rabbit aorta• The metabolic capabilities of the arterial wall have come under scrutiny in the past few years in attempts to elucidate the relationship of vessel wall metabolism to atherosclerosis (1)(2)(3)(4)(5)(6)(7)(8). Attention has been directed toward the endogenous lipid synthetic processes in blood vessels because of the possible role they may play in the accumulation of lipid substances in the atherosclerotic plaque (6,(8)(9)(10)(11). Although the synthesis of phospholipids has been demonstrated in blood vessels of both experimental animals and humans (2,9,(12)(13)(14)(15)(16)(17), the significance of the phospholipid synthetic mechanism is unknown. Zilversmit and his coworkers (18,19) have suggested that this synthesis is accelerated in experimental atherosclerosis and that this represents an effort on This work was supported by research grants from the Washington State Heart Association (6566-8) and U. S. Public Health Service (5 RO1 AM 08569-02, 2 RO1 AM 08368-09A1, AM 02456-07).Accepted for publication June 22, 1966. the part of the vascular wall to utilize the surface active properties of phospholipids to solubilize cholesterol accumulating in the plaque. The capacity of the vascular wall to synthesize phospholipids is apparently related to its ability to metabolize glucose, because recent investigations have suggested that the products of glycolysis and oxidation phosphorylation (a-glycerophosphate and ATP) are requirements for phosphatdde synthesis (15, 17).It has been proposed on morphological grounds that the cells responsible for this increased phospholipid metabolism are those accumulating in the intimal plaques (24). These cells have been variously labeled fibroblasts, monocytoid cells and macrophages, but recent electron microscopic studies have clearly identified one predominant cell type to be smooth muscle (24,25). In one of these studies (24), special attention was directed to the smooth muscle cells in the plaque (called myo-intimal cells) and the...

Cholesteryl Ester Synthesis in Normal and Atherosclerotic Aortas of Rabbits and Rhesus Monkeys

“…Parker et al (28) have observed a proliferation of endoplasmic reticulum in aortic smooth muscle cells as a result of cholesterol feeding. Portman and Alexander (29) have reported that the microsomal fraction from nonatherosclerotic aortic tissue largely contains plasma membrane fragments, which proliferate as a result of aging or hyperlipemia.…”

Uptake and Metabolism of 14 C-Labeled Oleic Acid by Atherosclerotic Lesions in Rabbit Aorta

“…Foam cells isolated from rabbit atherosclerotic lesions have also been shown to incorporate 32 P-labeled phosphate into phospholipid and to be responsible in part for the phospholipid synthesis in the atherosclerotic intima (16). Parker et al (17), in a combined biochemical-morphological study, have shown that rabbit atherosclerotic lesions take up and incorporate 780 DAY, WAHLQVIST linoleic acid into phospholipid and that the magnitude of such incorporation is related to the increasing number of myointimal cell membranous organelles present in the developing lesion. All of these studies indicate that foam cells may be responsible in part for the lipid synthesis which takes place in the atherosclerotic lesion, but direct evidence implicating these cells is not available.…”