Effect of pravastatin in mildly hypercholesterolemic young men on serum matrix metalloproteinases

Kalela, Anne; Laaksonen, Reijo; Lehtimäki, Terho; Koivu, Tommi A.; Höyhtyä, Matti; Janatuinen, Tuula; Pöllänen, Perttu J.; Vesalainen, Risto; Saikku, Pekka; Knuuti, Juhani; Nikkari, Seppo T.

doi:10.1016/s0002-9149(01)01616-2

Cited by 34 publications

(20 citation statements)

References 16 publications

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“…Most studies including patients with coronary artery disease have found statin-reducing effects on MMP expression [31,33], whereas studies on hypercholesterolemic individuals without known coronary artery disease have shown variable results [32,38,39]. In contrast to our study, the vast majority of these studies have neither been randomized, nor placebo controlled.…”

Section: Discussioncontrasting

confidence: 61%

Effects of Simvastatin on Proinflammatory Cytokines and Matrix Metalloproteinases in Hypercholesterolemic Individuals

Nilsson

Eriksson

Cherfan³

et al. 2010

Inflammation

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Statins are potent lipid-lowering drugs but anti-inflammatory effects have also been suggested. Our aim was to investigate the effects of simvastatin on proinflammatory cytokines and matrix metalloproteinases (MMPs). Eighty hypercholesterolemic men were randomized to simvastatin 40 mg or placebo for 6 weeks. Simvastatin treatment significantly reduced C-reactive protein (CRP) levels while interleukin (IL)-6 levels remained unchanged. The ex vivo release of IL-1β and IL-6 was not altered by simvastatin, whereas the release of TNF-α and IL-8 increased after 6 weeks of simvastatin treatment. Similarly, the circulating levels of MMP-3 and TIMP-1 remained unaffected by simvastatin while MMP-9 increased. However, none of the effects except for the CRP reduction within the simvastatin group reached statistical significance when compared to the placebo group. Our findings are in contrast to previous in vitro and animal data and question the in vivo relevance of some of the pleiotropic effects of simvastatin.

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Section: Discussioncontrasting

confidence: 61%

Effects of Simvastatin on Proinflammatory Cytokines and Matrix Metalloproteinases in Hypercholesterolemic Individuals

Nilsson

Eriksson

Cherfan³

et al. 2010

Inflammation

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“…7 This effect is not just confined to atherosclerosis, however, because a reduction in matrix metalloproteinase-9 in serum samples also has been observed in humans treated with pravastatin. 19 Therefore, statins were a logical choice for a potential therapy for Marfan syndrome.…”

Section: Discussionmentioning

confidence: 99%

Pravastatin Reduces Marfan Aortic Dilation

et al. 2011

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Background-The sequelae of aortic root dilation are the lethal consequences of Marfan syndrome. The root dilation is attributable to an imbalance between deposition of matrix elements and metalloproteinases in the aortic medial layer as a result of excessive transforming growth factor-beta signaling. This study examined the efficacy and mechanism of statins in attenuating aortic root dilation in Marfan syndrome and compared effects to the other main proposed preventative agent, losartan. Methods and Results-Marfan mice heterozygous for a mutant allele encoding a cysteine substitution in fibrillin-1 (C1039G) were treated daily from 6 weeks old with pravastatin 0.5g/L or losartan 0.6 g/L. The end points of aortic root diameter (nϭ25), aortic thickness, and architecture (nϭ10), elastin volume (nϭ5), dp/dtmax (maximal rate of change of pressure) (cardiac catheter; nϭ20), and ultrastructural analysis with stereology (electron microscopy; nϭ5) were examined.

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“…One study observed that pravastatin decreased serum MMP-9 levels independently of changes in lipid levels. 21 Recently, Williams et al 22 demonstrated that compared with arteries of monkeys not receiving pravastatin, the arteries of pravastatin-treated monkeys had better dilator function and plaque characteristics more consistent with plaque stability. Of interest, these beneficial arterial effects of pravastatin occurred independently of plasma lipoprotein concentrations, which were consistent with our data.…”

Section: Discussionmentioning

confidence: 99%

Comparative Effects of Diet and Statin on NO Bioactivity and Matrix Metalloproteinases in Hypercholesterolemic Patients With Coronary Artery Disease

Koh

Son

Ahn

et al. 2002

ATVB

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Objective-We investigated the effects of statin compared with the American Heart Association (AHA) Step I Diet on lipoproteins, vasomotor function, tumor necrosis factor (TNF)-␣, and serological markers of plaque stability. Furthermore, we investigated the mechanism of regulation suggested by experimental studies. Methods and Results-For 14 weeks, we administered AHA dietϩplacebo and AHA dietϩsimvastatin (20 mg daily) to 31 and 32 randomly selected patients with coronary artery disease, respectively. Compared with diet alone, simvastatin significantly improved the percent flow-mediated dilator response to hyperemia from 3.37Ϯ2.28% to 5.89Ϯ2.35% (PϽ0.001) and lowered plasma levels of C-reactive protein from 0.48 to 0.10 mg/dL (PϽ0.001), TNF-␣ from 3.38 to 2.79 pg/mL (PϽ0.001), total matrix metalloproteinase (MMP)-9 from 36 to 28 ng/mL (Pϭ0.006), and tissue inhibitor of matrix metalloproteinase-1 from 80Ϯ30 to 74Ϯ23 ng/mL (Pϭ0.041), and simvastatin lowered to a greater extent MMP-9 activity (from 71 to 52 ng/mL, Pϭ0.006) and MMP-9 activity/tissue inhibitor of matrix metalloproteinase-1 ratios (Pϭ0.018), although this difference did not reach statistical significance. There were significant correlations between the degree of changes in TNF-␣ and the degree of changes in MMP-9 activity (rϭ0.424, Pϭ0.016). However, no significant correlations between lipoprotein levels or flow-mediated dilation percentages and levels of plaque stability markers were determined (Ϫ0.208ՅrՅ0.243). Conclusions-Simvastatin

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Effect of pravastatin in mildly hypercholesterolemic young men on serum matrix metalloproteinases

Cited by 34 publications

References 16 publications

Effects of Simvastatin on Proinflammatory Cytokines and Matrix Metalloproteinases in Hypercholesterolemic Individuals

Effects of Simvastatin on Proinflammatory Cytokines and Matrix Metalloproteinases in Hypercholesterolemic Individuals

Pravastatin Reduces Marfan Aortic Dilation

Comparative Effects of Diet and Statin on NO Bioactivity and Matrix Metalloproteinases in Hypercholesterolemic Patients With Coronary Artery Disease

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