Statins Alter Smooth Muscle Cell Accumulation and Collagen Content in Established Atheroma of Watanabe Heritable Hyperlipidemic Rabbits

Fukumoto, Yoshihiro; Libby, Peter; Rabkin, Elena; Hill, Christopher C.; Enomoto, Makoto; Hirouchi, Yasuhiko; Shiomi, Masashi; Aikawa, Masanori

doi:10.1161/01.cir.103.7.993

Cited by 355 publications

(250 citation statements)

References 40 publications

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“…After this early phase, the increase in PWV tends to disappear and is even reversed as a consequence of the remodelling of the vascular wall. [10][11][12]28 Such experimental findings agree with the slight increase in PWV that we observed in the present study after the 12-week treatment.…”

Section: Commentssupporting

confidence: 93%

“…[8][9][10][11][12]28 Furthermore, in patients with hypercholesterolaemia, radial artery compliance was found to increase to a larger extent after a two-year treatment than after a six-month treatment of simvastatin. 15,29 Finally, all these findings taken together agree with the clinical observations that, although favourable changes in lesion composition were observed within three months of statin treatment, clinical trials suggest that event reduction takes six-twelve months after initiation of treatment.…”

Section: Commentsmentioning

confidence: 92%

“…3 Secondly, statins cause, at an early phase, a rapid reduction of lipid vascular content, and thereby may be responsible for an absolute or relative increase in collagen, a process causing an increase of arterial stiffness. [10][11][12] Finally, in subjects with hypercholesterolaemia, statin treatments are associated with either decreased or unchanged alterations of arterial stiffness. 13,14 In subjects with hypertension, the situation may be even more complex to evaluate since increased stiffness may be the consequence of both high blood pressure and intrinsic modifications of the arterial wall.…”

Section: Introductionmentioning

confidence: 99%

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Effects of atorvastatin on aortic pulse wave velocity in patients with hypertension and hypercholesterolaemia: a preliminary study

Rudnichi

2002

J Hum Hypertens

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As statins may contribute to plaque stabilisation, it is important to evaluate whether these drugs may modify arterial stiffness. In 23 patients, aged 32-70 years, with hypertension and hypercholesterolaemia, a doubleblind randomised study vs placebo was performed to evaluate whether atorvastatin was able to modify aortic stiffness, measured from aortic pulse wave velocity (PWV), after a 12-week treatment. The results revealed that atorvastatin did not change blood pressure, significantly lowered (Po0.003; o0.002) plasma total and LDL cholesterol, and increased aortic PWV by +8% (vs À2% under placebo) (P40.05). The percentage changes in plasma total and LDL cholesterol and in PWV were significantly and negatively correlated, independent of blood pressure level. The finding of increased aortic PWV after 12-week statin treatment agrees with studies in monkeys, indicating that, at the early phase of hypolipidaemic diet but not later, aortic PWV increases transiently as a consequence of the significant reduction of lipid vascular content. In conclusion, the present results support the possibility that statins might contribute to a change in arterial stiffness independent of blood pressure level, and suggest that long-term studies in humans are needed to evaluate the contribution of arterial elasticity to statin-induced vascular remodelling.

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Section: Commentssupporting

confidence: 93%

Section: Commentsmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Effects of atorvastatin on aortic pulse wave velocity in patients with hypertension and hypercholesterolaemia: a preliminary study

Rudnichi

2002

J Hum Hypertens

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“…15 The purpose of the present study was to determine the long-term effects of statins on BP control and PWV in hypertensive hyperlipidaemic patients undergoing antihypertensive therapy. Since recent in vivo studies in rabbits 16 and in vitro data [17][18][19] have indicated that hydrophilic and lipophilic statins have different effects on apoptosis, proliferation of vascular smooth muscle cells, and collagen production by vascular smooth muscle cells, in the present study we evaluated the effects of a hydrophilic drug, pravastatin, and two lipophilic drugs, simvastatin and fluvastatin, on the PWV of hypertensive patients with high serum cholesterol levels.…”

Section: Introductionmentioning

confidence: 99%

Long-term effects of statins on arterial pressure and stiffness of hypertensives

et al. 2004

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Although lowering blood pressure (BP) reduces aortic stiffness, achieving the recommended BP goal can be difficult. Recent studies have shown that short-term use of statins can reduce BP significantly. To determine the long-term effects of statins on BP and aortic stiffness, a single-blind randomized prospective study was performed on 85 hyperlipidaemic hypertensive patients whose BP was insufficiently controlled by antihypertensive therapy. Every 3 months, aortic stiffness was assessed by measuring pulse wave velocity (PWV). Patients were randomly allocated to groups treated with pravastatin, simvastatin, fluvastatin, or a nonstatin antihyperlipidaemic drug. No significant differences in patient characteristics, kinds of antihypertensive drugs, BP, ankle brachial index, PWV, or serum lipid, creatinine, or C-reactive protein levels were found between the four groups at the start of the study. During the 12-month treatment period, PWV did not change in the pravastatin group or nonstatin group, but it was transiently reduced in the simvastatin group and significantly decreased in the fluvastatin group, even though the doses of the statins used in this study were lower than the usually prescribed dose. All four antihyperlipidaemic drugs significantly decreased serum cholesterol levels without affecting BP, ankle brachial index, or serum triglyceride levels. The Creactive protein serum levels decreased significantly in the three statin groups but not in the nonstatin group. These results suggest that long-term use of fluvastatin by hyperlipidaemic hypertensive patients is associated with a significant reduction in aortic stiffness without any effect on BP.

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“…Decreased collagen content translates to less stable atherosclerotic plaques, capable of rupture with associated thrombosis and infarction (Libby & Aikawa, 2002). Increased collagen content and strength of the atherosclerotic plaque may also be part of the benefit afforded by lipid lowering (Aikawa et al, 1998) and statin (Fukumoto et al, 2001) therapies.…”

Section: Role Of Ascorbate In Preventing and Stabilizing Atheroscleromentioning

confidence: 99%

Inflammation in the vascular bed: Importance of vitamin C

Aguirre

May

2008

Pharmacology & Therapeutics

108

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Despite decreases in atherosclerotic coronary vascular disease over the last several decades, atherosclerosis remains a major cause of mortality in developed nations. One possible contributor to this residual risk is oxidant stress, which is generated by the inflammatory response of atherosclerosis. Although there is a wealth of in vitro, cellular, and animal data supporting a protective role for antioxidant vitamins and nutrients in the atherosclerotic process, the best clinical trials have been negative. This may be due to the fact that antioxidant therapies are applied "too little and too late." This review considers the role of vitamin C, or ascorbic acid in preventing the earliest inflammatory changes in atherosclerosis. It focuses on the three major vascular cell types involved in atherosclerosis: endothelial cells, vascular smooth muscle cells, and macrophages. Ascorbate chemistry, recycling, and function are described for these cell types, with emphasis on whether and how the vitamin might affect the inflammatory process. For endothelial cells, ascorbate helps to prevent endothelial dysfunction, stimulates type IV collagen synthesis, and enhances cell proliferation. For vascular smooth muscle cells, ascorbate inhibits dedifferentiation, recruitment, and proliferation in areas of vascular damage. For macrophages, ascorbate decreases oxidant stress related to their activation, decreases uptake and degradation of oxidized LDL in some studies, and enhances several aspects of their function. Although further studies of ascorbate function in these cell types and in novel animal models are needed, available evidence generally supports a salutary role for this vitamin in ameliorating the earliest stages of atherosclerosis.

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Statins Alter Smooth Muscle Cell Accumulation and Collagen Content in Established Atheroma of Watanabe Heritable Hyperlipidemic Rabbits

Abstract: This study showed that statins can reduce MMP expression in atheroma and that cell-permeant statins can decrease SMC number and collagen gene expression in vivo.

Cited by 355 publications

References 40 publications

Effects of atorvastatin on aortic pulse wave velocity in patients with hypertension and hypercholesterolaemia: a preliminary study

Effects of atorvastatin on aortic pulse wave velocity in patients with hypertension and hypercholesterolaemia: a preliminary study

Long-term effects of statins on arterial pressure and stiffness of hypertensives

Inflammation in the vascular bed: Importance of vitamin C

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