The Effect of Cortisone on the Serum Lipids and on the Development of Experimental Cholesterol Atherosclerosis in the Rabbit

Abstract

An experiment was performed to determine the effect of cortisone on the serum lipids and on the development of experimental cholesterol atherosclerosis in the rabbit. Litter mate rabbits of the same sex were employed; both sexes were represented in the experiment. The report is based upon four experimental groups comprising (1) 12 rabbits fed cholesterol and treated with cortisone vehicle; (2) 12 rabbits fed cholesterol and treated daily with cortisone; (3) 11 rabbits treated with cortisone; and (4) 7 rabbits that received cortisone vehicle. It was observed that: (1) There was less aortic atherosclerosis in the cholesterol-fed cortisone-treated rabbits as judged by both morphological and chemical means than in the rabbits fed cholesterol without cortisone treatment. (2) Cortisone depressed appreciably the hypercholesterolemia resulting from the feeding of cholesterol to rabbits. (3) Cortisone treatment caused a moderate hypercholesterolemia in normal rabbits. (4) Cortisone caused a moderate increase in serum lipid phosphorus equal to that produced by cholesterol feeding alone. (5) The combination of cholesterol feeding and cortisone did not result in a higher phospholipidemia than either one of these agents alone. (6) Cortisone caused a great increase in serum-neutral fat; it was not apparent whether cholesterol feeding affected the neutral fat lipemia due to cortisone treatment alone. (7) The total cholesterol to lipid phosphorus ratio was about normal in the rabbits that received cortisone only. It was doubled in the animals receiving both cholesterol and cortisone, and it was increased about four times in those that received only cholesterol. The significance of the alterations in the serum lipids induced by cortisone is discussed in relation to the inhibition of the development of aortic atherosclerosis that occurred in the cholesterol-fed rabbits treated with cortisone.

Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11β-hydroxysteroid dehydrogenase type 1

“…Whereas circulating glucocorticoids correlate positively with CVD in humans [9,10], animal studies (e.g. on rabbits and dogs) suggest an atheroprotective role of both natural and synthetic glucocorticoids [8,11]. An excess of glucocorticoids, as in Cushing's syndrome or with the pharmacological therapy common in autoimmune diseases, is associated with an increase in atherosclerotic and cardiovascular events [12,13].…”

Glucocorticoid Resistance Caused by Reduced Expression of the Glucocorticoid Receptor in Cells From Human Vascular Lesions

“…In cholesterol models of atherosclerosis, treatment with hydrocortisone has consistently been shown to lessen the severity of atherosclerosis in various rabbit models. [17][18][19][20] In models of balloon-catheter injury, GCs typically inhibit neointimal proliferation in vivo in both rat 21 and rabbit models, [22][23][24] although shorter, 1-week treatments with dexamethasone have failed to inhibit intimal hyperplasia in rabbits. 25 Despite these in vivo effects of steroids, 2 clinical trials have failed to observe a beneficial role of GCs in preventing restenosis in humans.…”

Both Transient and Continuous Corticosterone Excess Inhibit Atherosclerotic Plaque Formation in APOE*3-Leiden.CETP Mice

“…Human data show an association between increased GC secretion and cardiovascular disease even after long-term successful correction of GC excess [6], whereas previous studies in animals, e.g. rabbits [7], [8], [9], [10], [11] and dogs [12] using either natural or synthetic GC, suggest an atheroprotective role of GC. On the other hand, 11β-dehydrogenase type 2 (11βHSD2) deficient mice, in which the activation of the mineralocorticoid receptor (MR) by GCs cannot be prevented, have an increased atherosclerotic plaque development [13], suggesting that increased activation of the MR promotes atherosclerotic plaque formation.…”