Statins differentially regulate vascular endothelial growth factor synthesis in endothelial and vascular smooth muscle cells

Frick, Matthias; Dulak, Józef; Cisowski, Jaroslaw; Józkowicz, Alicja; Zwick, Ralf Harun; Alber, Hannes; Dichtl, Wolfgang; Schwarzacher, Severin P.; Pachinger, Otmar; Weidinger, Franz

doi:10.1016/s0021-9150(03)00299-5

Cited by 93 publications

(78 citation statements)

References 31 publications

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“…Given these diverse pathways and anatomically distant events, what evidence exists to suggest that statin therapy (or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) might affect any of these pathological events? Matrix remodelling MM Reduced lung parenchymal destruction and MMP 9 activity in smoke exposed rat lung [74,75] HM ex vivo (bronchial epithelial Increase apoptosis in human vascular endothelial cells [84,86] Oxidant response HM in vivo (PMN) Reduce IL-8 release from neutrophils and neutrophil derived reactive oxidant species [77] HM in vivo (serum), MM Strong anti-oxidant properties [87,88] Mucus production MM Reduced LPS-induced goblet cell hyperplasia in bronchial epithelium and Muc5A induced mucus hypersecretion community acquired pneumonia (table 2) [102][103][104][105][106][107][108][109]. However, unlike the studies in COPD, the results in pneumonia are not consistent.…”

Section: Copd and Systemic Inflammationmentioning

confidence: 99%

Pharmacological actions of statins: potential utility in COPD

Young

Hopkins²,

Eaton³

2009

European Respiratory Review

122

184

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Chronic obstructive pulmonary disease (COPD) is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance) and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-kB mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1) Inhibition of cytokine production (tumour necrosis factor-a, interleukin (IL)-6 and IL-8) and neutrophil infiltration into the lung; 2) inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3) antioxidant and anti-inflammatory (IL-6 mediated) effects on skeletal muscle; 4) reduced inflammatory response to pulmonary infection; and 5) inhibition of the development (or reversal) of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD.

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Section: Copd and Systemic Inflammationmentioning

confidence: 99%

Pharmacological actions of statins: potential utility in COPD

Young

Hopkins²,

Eaton³

2009

European Respiratory Review

122

184

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“…57 The effect of statins on the induction of angiogenesis, however, is dose dependent and biphasic. 58 Some authors particularly highlight the proangiogenic effects of statins caused by low, nanomolar concentrations and regarded as beneficial for the treatment of vascular diseases. 58 Others have found that a high dose of statins promotes endothelial cell death and inhibits experimental angiogenesis induced by growth factors or tumor, laying a foundation for developing statin-based angiopreventive strategies.…”

Section: Pharmacological Treatment Of Stroke Statinsmentioning

confidence: 99%

“…58 Some authors particularly highlight the proangiogenic effects of statins caused by low, nanomolar concentrations and regarded as beneficial for the treatment of vascular diseases. 58 Others have found that a high dose of statins promotes endothelial cell death and inhibits experimental angiogenesis induced by growth factors or tumor, laying a foundation for developing statin-based angiopreventive strategies. 59 In addition to their effects on cerebrovascular function, statins increase neurogenesis in ischemic brain, protect cortical neurons from excitotoxicity, and increase neurite outgrowth and synaptic plasticity.…”

Section: Pharmacological Treatment Of Stroke Statinsmentioning

confidence: 99%

Neurorestorative treatment of stroke: Cell and pharmacological approaches

Chen

Chopp

2006

NeuroRX

153

114

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Summary:There is a compelling need to develop cell and pharmacological therapeutic approaches to be administered beyond the hyperacute phase of stroke. These therapies capitalize on the capacity of the brain for neuroregeneration and neuroplasticity and are designed to reduce neurological deficits after stroke. This review provides an update of bone marrowderived mesenchymal stem cells (MSCs) and select pharmacological agents in clinical use for other indications that promote the recovery process in the subacute and chronic phases after stroke. Among these agents are 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors (statins), erythropoietin (EPO), and phosphodiesterase type 5 (PDE-5) inhibitors and nitric oxide (NO) donors. Both the MSCs and the pharmacologic agents potentiate brain plasticity and neurobehavioral recovery after stroke.

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“…Isolation of RNA, synthesis of cDNA and PCR was performed as described [7]. The primers recognizing HO-1: (5′GTG GAG ACG CTT TAC GTA GTG C and 5′CTT TCA GAA GGG TCA GGT GTC C), eNOS (5′-GTG ATG GCG AAG CGA GTG AA and 5′-CCG AGC CCG AAC ACA CAG AA) and EF2 (5′-GCG GTC AGC ACA ATG GCA TA and 5′-GAC ATC ACC AAG GGT GTG CAG) as a reporter gene have been used.…”

Section: Reverse Transcription-polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Atorvastatin prevents hypoxia-induced inhibition of endothelial nitric oxide synthase expression but does not affect heme oxygenase-1 in human microvascular endothelial cells

et al. 2006

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Beneficial cardiovascular effects of statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are particularly assigned to the modulation of inflammation. Endothelial nitric oxide synthase (eNOS) and heme oxygenase-1 (HO-1) are listed among the crucial protective, anti-inflammatory genes in the vasculature. Here we show that atorvastatin at pharmacologically relevant concentration (0.1 μM) enhanced the expression of eNOS in human microvascular endothelial cells (HMEC-1). Moreover, atorvastatin prevented hypoxia-induced decrease in eNOS expression. However, in the same cells atorvastatin was ineffective in modulation of HO-1 protein level. Therefore, we suggest that the protective effect of statins at their pharmacological concentrations is not mediated by enhancement of HO-1 activity, but may involve eNOS.

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Statins differentially regulate vascular endothelial growth factor synthesis in endothelial and vascular smooth muscle cells

Cited by 93 publications

References 31 publications

Pharmacological actions of statins: potential utility in COPD

Pharmacological actions of statins: potential utility in COPD

Neurorestorative treatment of stroke: Cell and pharmacological approaches

Atorvastatin prevents hypoxia-induced inhibition of endothelial nitric oxide synthase expression but does not affect heme oxygenase-1 in human microvascular endothelial cells

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