Safety and efficacy of statin therapy

Adhyaru, Bhavin; Jacobson, Terry A.

doi:10.1038/s41569-018-0098-5

Cited by 285 publications

(223 citation statements)

References 88 publications

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“…The two groups differ in their ability to inhibit HMGCR and in their lipophilicity [26]. Statins show numerous pleiotropic effects including anti-in ammatory, anti-angiogenic, anti-oxidant and anticancer activities [27]. Multiple pleiotropic anti-cancer effects were observed such as induction of cell cycle arrest, apoptosis, inhibition of migration, invasion, metastasis and angiogenesis [28,29] and particularly, a cytotoxic effect was reported in hematological malignancies [30,31].…”

Section: Discussionmentioning

confidence: 99%

Network-Based Drug Discovery Identifies Statins as a Repurposing Agent to Improve Activity of Current Therapies in Chronic Lymphocytic Leukemia.

Giménez

Tripathi

Giró

et al. 2020

Preprint

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Background: Chronic lymphocytic leukemia (CLL) is a B lymphoid malignancy highly dependent on the microenvironment. CLL cell interactions with the supportive tissue microenvironment play a critical role in disease pathogenesis. Despite new targeted therapies such as ibrutinib and venetoclax, disease progression and relapse remain an issue. The present study aimed to identify drugs targeting key proteins described to have a role in the microenvironment.Methods: We used a platform for drug discovery based on systems biology and artificial intelligence. Bioactive compounds have been screened in silico and selected compounds were evaluated in CLL cell lines in the presence of stromal cells to mimic the microenvironment and validated the best candidates in primary CLL cells. Results: Our results showed that the commercial drug simvastatin was the most effective and selective out of the tested compounds. Simvastatin decreased CLL cell survival and proliferation as well as cell adhesion. Importantly, this drug enhanced the antitumor effect of venetoclax and ibrutinib. Conclusions: We proposed that systems biology approaches combined with pharmacology screening could help to find new drugs for CLL treatment and to predict new combinations with current therapies. Our results highlight the possibility of repurposing widely used drugs such as statins to target the microenvironment and to improve the efficacy of ibrutinib or venetoclax in CLL cells.

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Section: Discussionmentioning

confidence: 99%

Network-Based Drug Discovery Identifies Statins as a Repurposing Agent to Improve Activity of Current Therapies in Chronic Lymphocytic Leukemia.

Giménez

Tripathi

Giró

et al. 2020

Preprint

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“…Statins are very liberally used for their anti-inflammatory and lipid-controlling properties. 1 Some other statinrelated features are associated with protein degradation during skeletal muscle myopathy, 1 amyloid formation, 2 and even cancer. 3 Would it be possible to harness statinrelated protein degradation to treat aortic valve calcification and stenosis once the degenerative cardiovascular process has already commenced?…”

Section: Commentary: Reversibility Of Aortic Valve Stenosis?mentioning

confidence: 99%

Commentary: Reversibility of aortic valve stenosis?

Mennander

2021

The Journal of Thoracic and Cardiovascular Surgery

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“…Firstly, the relatively high price of treatment with PCSK9 inhibitors makes them cost ineffective and hinders their widespread use 27 . Secondly, little is known to date about the long‐term tolerance of these drugs due to their recent approval 28 . Future studies will add more detail on the PCSK9 inhibitors safety and effectiveness, allowing for a better positioning of these drugs within the spectrum of antiatherosclerosis and antihyperlipidemia treatments.…”

Section: Current Cardiovascular Disease Management Strategiesmentioning

confidence: 99%

Lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy

Zakirov

Zhang

Grechko

et al. 2020

Pharmacology Res & Perspec

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Atherosclerosis with associated cardiovascular diseases remains one of the main causes of disability and death worldwide, requiring development of new solutions for prevention and treatment. Macrophages are the key effectors of a series of events involved in atherogenesis, such as inflammation, plaque formation, and changes in lipid metabolism. Some of these events were shown to be associated with mitochondrial dysfunction and excessive mitochondrial DNA (mtDNA) damage. Moreover, macrophages represent a promising target for novel therapeutic approaches that are based on the expression of various receptors and nanoparticle uptake. Lipid‐based gene delivery to mitochondria is considered to be an interesting strategy for mtDNA damage correction. To date, several nanocarriers and their modifications have been developed that demonstrate high transfection efficiency and low cytotoxicity. This review discusses the possibilities of lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy.

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Safety and efficacy of statin therapy

Cited by 285 publications

References 88 publications

Network-Based Drug Discovery Identifies Statins as a Repurposing Agent to Improve Activity of Current Therapies in Chronic Lymphocytic Leukemia.

Network-Based Drug Discovery Identifies Statins as a Repurposing Agent to Improve Activity of Current Therapies in Chronic Lymphocytic Leukemia.

Commentary: Reversibility of aortic valve stenosis?

Lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy

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