Expanding the pleiotropic effects of statins: attenuation of air pollution-induced inflammatory response

Tasat, Deborah Ruth; Yakisich, Juan Sebastián

doi:10.1152/ajplung.00280.2012

Cited by 5 publications

(4 citation statements)

References 16 publications

(16 reference statements)

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“…Simvastatin has protective effects against oxidative stress, matrix metalloproteinase, and inflammation in preclinical studies (28). Statins also show potential uses in chronic obstructive pulmonary disease, osteoporosis, diabetes, and depression (42). The safety and efficacy of cholesterol-lowering drug statins are well documented as highly effective therapies used by millions of people (24,38).…”

Section: Discussionmentioning

confidence: 99%

Statins in Lymphangioleiomyomatosis. Simvastatin and Atorvastatin Induce Differential Effects on tuberous sclerosis complex 2–Null Cell Growth and Signaling

Atochina‐Vasserman

Goncharov

Volgina

et al. 2013

Am J Respir Cell Mol Biol

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Mutations of the tumor suppressor genes tuberous sclerosis complex (TSC)1 and TSC2 cause pulmonary lymphangioleiomyomatosis (LAM) and tuberous sclerosis (TS). Current rapamycin-based therapies for TS and LAM have a predominantly cytostatic effect, and disease progression resumes with therapy cessation. Evidence of RhoA GTPase activation in LAM-derived and human TSC2-null cells suggests that 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor statins can be used as potential adjuvant agents. The goal of this study was to determine which statin (simvastatin or atorvastatin) is more effective in suppressing TSC2-null cell growth and signaling. Simvastatin, but not atorvastatin, showed a concentration-dependent (0.5-10 μM) inhibitory effect on mouse TSC2-null and human LAM-derived cell growth. Treatment with 10 μM simvastatin induced dramatic disruption of TSC2-null cell monolayer and cell rounding; in contrast, few changes were observed in cells treated with the same concentration of atorvastatin. Combined treatment of rapamycin with simvastatin but not with atorvastatin showed a synergistic growth-inhibitory effect on TSC2-null cells. Simvastatin, but not atorvastatin, inhibited the activity of prosurvival serine-threonine kinase Akt and induced marked up-regulation of cleaved caspase-3, a marker of cell apoptosis. Simvastatin, but not atorvastatin, also induced concentration-dependent inhibition of p42/p44 Erk and mTORC1. Thus, our data show growth-inhibitory and proapoptotic effects of simvastatin on TSC2-null cells compared with atorvastatin. These findings have translational significance for combinatorial therapeutic strategies of simvastatin to inhibit TSC2-null cell survival in TS and LAM.

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Section: Discussionmentioning

confidence: 99%

Statins in Lymphangioleiomyomatosis. Simvastatin and Atorvastatin Induce Differential Effects on tuberous sclerosis complex 2–Null Cell Growth and Signaling

Atochina‐Vasserman

Goncharov

Volgina

et al. 2013

Am J Respir Cell Mol Biol

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“…COPD patients with CVD receive additional lipid-lowering drugs such as statins, which inhibit the rate-controlling enzyme of cholesterol synthesis, 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase. Various murine studies have showed beneficial effects of statin therapy on the lungs, which is most likely mediated by its anti-inflammatory actions (237) in both acute and chronic disease states; for example, during sepsis after Streptococcus-induced acute lung injury (255), but also air pollution-induced pulmonary inflammation (210). Statins also result in lower acute CS-induced inflammation and oxidative stress (63), and elastase-induced emphysema is reduced upon statin treatment in WT mice (204).…”

Section: Treatment Of Copd Patients and Atherosclerosismentioning

confidence: 99%

Murine models of cardiovascular comorbidity in chronic obstructive pulmonary disease

Khedoe

Rensen

Berbée

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Patients with chronic obstructive pulmonary disease (COPD) have an increased risk for cardiovascular disease (CVD). Currently, COPD patients with atherosclerosis (i.e., the most important underlying cause of CVD) receive COPD therapy complemented with standard CVD therapy. This may, however, not be the most optimal treatment. To investigate the link between COPD and atherosclerosis and to develop specific therapeutic strategies for COPD patients with atherosclerosis, a substantial number of preclinical studies using murine models have been performed. In this review, we summarize the currently used murine models of COPD and atherosclerosis, both individually and combined, and discuss the relevance of these models for studying the pathogenesis and development of new treatments for COPD patients with atherosclerosis. Murine and clinical studies have provided complementary information showing a prominent role for systemic inflammation and oxidative stress in the link between COPD and atherosclerosis. These and other studies showed that murine models for COPD and atherosclerosis are useful tools and can provide important insights relevant to understanding the link between COPD and CVD. More importantly, murine studies provide good platforms for studying the potential of promising (new) therapeutic strategies for COPD patients with CVD.

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“…There is some evidence to support this idea (Grievink et al 1999). Alternatively, it might be possible to oppose the effects of particles by medication: there is some evidence to show that statins reduce the inflammatory effects of PM (Tasat and Yakisich 2012). In addition, if we knew the number of people affected, it would be possible to calculate more accurately the extent of the effects they suffer.…”

Section: The Toxicological Puzzlementioning

confidence: 99%

The effects on health of ambient particles: time for an agonizing reappraisal?

Maynard

2015

Cell Biol Toxicol

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Expanding the pleiotropic effects of statins: attenuation of air pollution-induced inflammatory response

Cited by 5 publications

References 16 publications

Statins in Lymphangioleiomyomatosis. Simvastatin and Atorvastatin Induce Differential Effects on tuberous sclerosis complex 2–Null Cell Growth and Signaling

Statins in Lymphangioleiomyomatosis. Simvastatin and Atorvastatin Induce Differential Effects on tuberous sclerosis complex 2–Null Cell Growth and Signaling

Murine models of cardiovascular comorbidity in chronic obstructive pulmonary disease

The effects on health of ambient particles: time for an agonizing reappraisal?

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