Effects of Etidronate and Lovastatin on the Regression of Atherosclerosis in Cholesterol-Fed Rabbits

Abstract

Eighty New Zealand rabbits in eight groups (10 each) were fed a 0.5% cholesterol diet for 12 weeks. One group served as a control and was sacrificed at the end of 12 weeks. Seven other groups were shifted to a normal diet and received a drug(s) or placebo for the second 12 weeks. The high dose of etidronate (3 mg/kg/day) with lovastatin (6 mg/kg/day) significantly reduced the percent of aortic atherosclerotic lesions [56 ± 21 vs. 77 ± 17% (mean ± SD), p < 0.05] in the regression study. Compared to the control groups for etidronate and lovastatin, the high or low dose (0.15 mg/kg/day) of etidronate significantly reduced aortic standardized plaque volume per unit (18.7 ± 7.9 or 18.8 ± 9.1 vs. 28.4 ± 11.8 mm·%, p < 0.05). Lovastatin reduced pulmonary artery maximum plaque thickness (0.13 ± 0.10 vs. 0.23 ± 0.11mm, p < 0.05). There were no differences in serum lipid and calcium levels in the control and treated groups. The high dose of etidronate inhibited bone mineralization as expected, whereas the low dose of etidronate did not. These data suggest that etidronate with lovastatin can regress aortic atherosclerosis in the cholesterol-fed rabbit placed on a normal diet.

Inhibition of Arterial Thrombus Formation by ApoA1 Milano

“…1,2 Experimental and clinical studies have shown reduction in atherosclerosis and cardiac events with aggressive lowering of serum total and LDL cholesterol levels. [3][4][5] Epidemiological studies also show an inverse relationship between the plasma levels of HDL cholesterol and atherosclerosis. 6,7 Plasma levels of apoA1, the major protein component of HDL cholesterol, are reduced in patients with premature coronary artery disease.…”

Complete Atherosclerosis Regression After Human ApoE Gene Transfer in ApoE-Deficient/Nude Mice

“…The concept of atherosclerosis regression remains a major challenge and has been approached in animal models and in humans during lipid-lowering drug trials. However, studies in both cholesterol fed-animals [1][2][3][4] and humans [5][6][7][8] lasted for several years and were difficult to manage owing to the variability of the results, and the regression, if it occurred, was marginal.…”

The Possible Influence of Bisphosphonate Therapy and Its Combination With Statins on Parameters of Aortic Stiffness in Women With Postmenopausal Osteoporosis

“…так, в исследо-ваниях показано влияние бисфосфонатов на процессы атеро-склероза [3][4][5], а статинов на костную ткань [6][7][8][9], вероятно,за счет их общего механизма действия через метаболический путь холестерина. ингибируя фермент гмг-коа-редуктазу, статины,с одной стороны, оказывают гиполипидемический эффект, с другой -могут приводить к подавлению функцио-нирования остеокластов, оказывая антирезорбтивный эффект [10].…”

“…Этидронат был первым бисфосфонатом, прием которого привел к снижению формирования асб в ар-териях кроликов, находящихся на высоко-калорийной диете и терапии препаратами витамина д без изменения уровня каль-ция сыворотки крови [47]. Экспериментальные исследования этидроната, памидроната и клодроната показали ингибирова-ние процессов атеросклероза без влияния на уровень липидов крови [3,48,49]. в литературе имеется всего несколько работ по изучению влияния бисфосфонатов на эластичность сосу-ОРИГИНАлЬНыЕ СТАТЬИ № 3/2014 Остеопороз и остеопатии дистой стенки.…”