Suppression of Calcific Fibrous-Fatty Plaque Formation in Rabbits by Agents Not Affecting Elevated Serum Cholesterol Levels: The Effect of Thiophene Compounds

We tested the suppressive effect of antihypercalcemic-hyperphosphatemic agents on atherogenesis. We studied five groups of rabbits for 8 weeks, one control group and four groups on a fibrogenic atherogenic diet. One group received the atherogenic diet alone, and the remaining three atherogenic group...

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Bibliographic Details
Published in:Circulation research 1978-07, Vol.43 (1), p.115-125
Main Authors: CHAN, CATHERINE T, WELLS, HERBERT, KRAMSCH, DIETER M
Format: Article
Language:English
Subjects:
Animals
Aorta, Abdominal - pathology
Aorta, Thoracic - pathology
Arteriosclerosis - drug therapy
Arteriosclerosis - pathology
Arteriosclerosis - prevention & control
Calcium - blood
Cholesterol - blood
Diet, Atherogenic
Fatty Liver - pathology
Phosphorus - blood
Rabbits
Thiophenes - therapeutic use
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Summary:We tested the suppressive effect of antihypercalcemic-hyperphosphatemic agents on atherogenesis. We studied five groups of rabbits for 8 weeks, one control group and four groups on a fibrogenic atherogenic diet. One group received the atherogenic diet alone, and the remaining three atherogenic groups were treated simultaneously with 2-thiophenecarboxylic acid (ThCA), 5-methyl-2- thiophenecarboxylic acid (5-CH3-ThCA), and 5-bromo-2-thiophenecarboxaldehyde (5-Br-ThCA). Rabbits receiving the atherogenic diet alone developed(1) elevations of serum cholesterol, calcium, and phosphorus; (2) massive fibrous-fatty aortic plaques with excessive accumulation of aortic collagen, elastin, and lipids; (3) marked deposition of calcium and phosphorus in both aortic tissue and elastin; and (4) severe lipid infiltration of the liver. Treatment with all three drugs normalized the elevated serum calcium but not the cholesterol levels, and effectively inhibited all aspects of the atherosclerotic process as determined morphologically and biochemically. The order of effectiveness was5-CH3- ThCA > 5-Br-ThCA > ThCA. No bone resorption occurred in the treated groups. The normalizing effects of the thiophene compounds on serum phosphorus levels were not significant at the dosages used.
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.43.1.115