TREATMENT OF HYPERLIPIDAEMIA RETARDS PROGRESSION OF SYMPTOMATIC FEMORAL ATHEROSCLEROSIS A Randomised Controlled Trial

Duffield, R. G. M.; Lewis, Barry; Miller, N. E.; Jamieson, C. W.; Brunt, J. N. H.; Colchester, Alan C. F.

doi:10.1016/s0140-6736(83)92527-8

Cited by 234 publications

(46 citation statements)

References 15 publications

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“…27 In the current study, feeding of a high-cholesterol diet to rabbits for 10 weeks resulted in marked hypercholesterolemia and development of atherosclerosis, which is consistent with several previous reports. [12][13][14] These findings confirm an important role for hypercholesterolemia in atherogenesis.…”

Section: Discussionsupporting

confidence: 93%

Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits

Yang

Phillips

Mohuczy

et al. 1998

ATVB

121

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Abstract-Angiotensin II (Ang II) promotes vascular smooth muscle growth and may be involved in the initiation and progression of atherosclerosis. To examine whether Ang II receptor expression in vascular tissues is altered in atherosclerosis, male New Zealand White rabbits were fed a high-cholesterol diet (1% cholesterolϩ4% coconut oil mixed with regular chow; hypercholesterolemic group, nϭ12) or regular chow (control group, nϭ8) for 10 weeks. At the end of this period, the serum cholesterol level in the rabbits fed the high-cholesterol diet was higher than that in the control group (3616Ϯ144 versus 30Ϯ1 mg/dL, PϽ0.001). There was no atherosclerosis in the aortas of the control group, whereas 51Ϯ6% of the aorta was covered with atherosclerosis in the hypercholesterolemic group. Total Ang II receptor expression in the atherosclerotic aortic tissues was increased 5-fold in the hypercholesterolemic rabbits (292Ϯ28 versus 51Ϯ32 fmol/mg tissue, meanϮSE, PϽ0.001), and the increased Ang II receptor expression was entirely due to enhanced Ang II type 1 (AT 1 ) receptor expression (289Ϯ38 versus 38Ϯ18 fmol/mg, PϽ0.001), as Ang II type 2 receptor expression was unaltered (7Ϯ5 versus 3Ϯ2 fmol/mg, PϭNS). AT 1 receptors were localized primarily in the media and to some extent in the intima of the atherosclerotic aorta, as determined by immunohistochemistry with specific monoclonal and polyclonal AT 1 receptor antibodies. Increased synthesis of AT 1 receptor mRNA in atherosclerotic tissues was confirmed by reverse transcription-polymerase chain reaction. To evaluate the functional significance of increased AT 1 receptor expression, the constrictor response of aortic rings to Ang II was examined and found to be markedly enhanced in atherosclerotic aortic rings (PϽ0.01 versus control aortic rings). The endotheliumdependent relaxation of aortic rings from hypercholesterolemic rabbits was markedly attenuated (PϽ0.001). This study shows that hypercholesterolemia in rabbits results in atherosclerosis, loss of endothelium-dependent relaxation, and increased Ang II receptor (entirely AT 1 receptor) expression in aortic tissues, which may result in altered vasoreactivity.

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Section: Discussionsupporting

confidence: 93%

Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits

Yang

Phillips

Mohuczy

et al. 1998

ATVB

121

View full text Add to dashboard Cite

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“…In previous work we have defined the relationship between vessel size and FMD in systemic arteries in humans and found that the diameter of the SFA in children is within the optimal range for resolution and response ( 17 (51)(52)(53). In early disease, cholesterol-lowering therapy might be beneficial if it was associated with an improvement in endothelial function.…”

Section: Resultsmentioning

confidence: 99%

Impairment of endothelium-dependent dilation is an early event in children with familial hypercholesterolemia and is related to the lipoprotein(a) level.

Celermajer²,

et al. 1994

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Familial hypercholesterolemia is associated with premature atherosclerosis. Since endothelial dysfunction is an early event in atherogenesis, we used a noninvasive method to assess endothelial function in the systemic arteries of 30 children aged 7-17 yr (median 11 ) with familial hypercholesterolemia (2 homozygotes, 28 heterozygotes, total cholesterol 240-696 mg/ dl) and 30 healthy age-and sex-matched controls. Using high resolution ultrasound, the diameter of the superficial femoral artery was measured at rest, in response to reactive hyperemia (with increased flow causing endothelium-dependent dilation), and after sublingual glyceryltrinitrate (causing endothelium-independent vasodilation).Flow-mediated dilation was present in the controls (7.5±0.7%) but was impaired or absent in the hypercholesterolemic children (1.2±0.4%, P < 0.0001). Total cholesterol was inversely correlated with flow-mediated dilation (r = -0.61, P < 0.0001). In the hypercholesterolemic children, flow-mediated dilation was inversely related to the lipoprotein(a) level (r = -0.61, P = 0.027) but not to other lipid fractions. Glyceryltrinitrate-induced dilation was present in all subjects but was lower in the hypercholesterolemia group (10.0±0.6% vs 12.4±0.8%, P = 0.023).Thus, impaired endothelium-dependent dilation is present in children with familial hypercholesterolemia as young as 7 yr of age and the degree of impairment is related to the lipoprotein(a) level. (J. Clin. Invest. 1994. 93:50-55.)

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“…3 Moreover, recent work has confirmed that such therapy results in improved survival not only in patients with established coronary heart disease, 4 but also in asymptomatic men with mild or moderate hypercholesterolaemia. 5 We describe a case in which agressive lipid lowering therapy with an HMG CoA reductase inhibitor was associated with the regression of an atherosclerotic plaque of the renal artery.…”

Section: Introductionmentioning

confidence: 98%

Regression of atherosclerotic renal artery stenosis with aggressive lipid lowering therapy

Khong

Missouris

et al. 2001

J Hum Hypertens

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TREATMENT OF HYPERLIPIDAEMIA RETARDS PROGRESSION OF SYMPTOMATIC FEMORAL ATHEROSCLEROSIS A Randomised Controlled Trial

Cited by 234 publications

References 15 publications

Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits

Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits

Impairment of endothelium-dependent dilation is an early event in children with familial hypercholesterolemia and is related to the lipoprotein(a) level.

Regression of atherosclerotic renal artery stenosis with aggressive lipid lowering therapy

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