Connective‐tissue reactions to implantation of purified sterol, sterol esters, phospho‐glycerides, glycerides and free fatty acids

Abstract

THE response of connective tissues to lipid deposition has been the subject of several investigations. Hass (1938) observed that cod-liver oil provokes an eosinophilic and giantcell response in subcutaneous tissue. Subsequently the injected material was converted into a lipofuscin-like substance. Hirsch (1938) found that intravenous injection of a cholesterol-fat mixture causes a giant-cell and fibroblastic reaction in the lungs and connective tissues; cholesterol acetate stimulates a similar giantcell response (Day and French, 1961). Spain (1961) observed that subcutaneous implantation of free cholesterol or desmosterol provokes an inflammatory response and fibrosis. Later it was noted that tripalmitin, tristearin and cholesterol esters are fibrogenic (Spain and Aristizabal, 1962). Hirsch and Weinhouse (1940) noted that emulsified cholesterol esters are inert and are resorbed by the reticuloendothelial system, but nonemulsified esters are intensely sclerogenic. A d a m et al. (1963) confirmed that cholesterol provokes a giantcell reaction and has a sclerogenic action on subcutaneous connective tissues, and found that these effects were prevented by adding phospholipids (lecithin or sphingomyelin) to the cholesterol implant. Later, Adams and Morgan (1967) confirmed with radioisotopes that phospholipid accelerates the resorption of 4-14C-cholesterol from subcutaneous implants; this effect depends upon both the surface active groups and the unsaturated fatty acids of phospholipids. METHODS Implantation of lipiak.Fifty-four male albino rats of weight 280-300 g. were used. The fur on the anterior abdominal wall was removed with a depilating cream and lipids were implanted aseptically under the skin of each quadrant. Solid lipids were inserted with a trocar and cannula (see Adams et af., 1963), whilst liquid lipids were injected with a 1-ml. syringe and widebore needle. The animals were killed so as to enable each lipid to be studied at intervals of 4 days, and 1,2,3,4+ and 6 wk after implantation; the lesions were exposed, measured, I. mni. BACT.-VOL. 94 rig69 63

Choroidal Vessel Wall: Hypercholesterolaemia-Induced Dysfunction and Potential Role of Statins

“…This increase in collagen fibres was also found in the intima, among VSMC and in the adventitia ( Figure 12C) of the large-and medium-sized-vessel layer and in the basal membrane of the EC of the choriocapillaris [6]. It is well known that the reabsorption of both esterified and free cholesterol is followed by intense sclerogenic activity [175], due to the capacity of cholesterols and their esters to induce inflammation. Some inflammatory cytokines (TNFα and IL-1) control the remodelling activity of macrophages and smooth-muscle cells, which have the capacity to produce several matrix metalloproteinases (MMPs) [176,177].…”

“…However, it should be men-tioned that an increase in collagen fibres in the vascular adventitia and in the intervascular spaces, and even fibroblast containing clumps of lipids could still be detected ( Figures 11D,12D). These features can be explained firstly by the low lipid-decreasing capability of statins at the dosage of 2 mg/kg/day used in the study and, secondly, to macrophage activity and their ability to produce MMPs [176,177] in the areas of higher concentrations of foam cells, where esterified and free-cholesterol reabsorption is followed by sclerogenic activity [175]. In hypercholesterolaemic New Zealand rabbits, treatment with fluvastatin sodium and pravastatin sodium at a dose (2mg/Kg/day) insufficient to normalize plasma-lipid levels prevents the progression of atherosclerosis in the different vascular layers of the choroid; the most striking effects being seen in EC and VSMC.…”

The pathology of idiopathic retroperitoneal fibrosis

“…However, medial aortic damage was often severe in the present series, and atheromatous material protruded into the adventitia in some cases. Some of the lipids in atherosclerotic plaques are undoubtedly fibrogenic (Abdulla, Adams, and Morgan, 1967), but the frequency of such adventitial protrusions in patients with no periaortic fibrosis probably excludes this as a simple cause. It would also be difficult to explain the characteristic inflammatory response on this basis alone.…”

Evidence for altered positional specificity of LCAT in vivo

“…Another consequence of the altered positional specificity of LCAT is the formation of saturated CE. Previous studies reported that the saturated CEs are more atherogenic than unsaturated CEs (31). Our earlier studies showed that the alteration in positional specificity of LCAT is seen mainly in animal species known to be susceptible to atherosclerosis (e.g., rabbit, human, pig, guinea-pig), whereas LCATs from the resistant species such as rat and mouse do not show this alteration (3,4).…”