Polymorphisms of the apolipoprotein E gene affect response to atorvastatin therapy in acute ischemic stroke

Bi, Qianqian; Zhou, X. R.; Lu, YanQin; Wang, Fu; Wang, YongPeng; Wang, Rui; Wang, Jue

doi:10.3389/fcvm.2022.1024014

Cited by 6 publications

(1 citation statement)

References 29 publications

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“…Interestingly, changes in protein expression in the high response lines include increased expression of HMGCR and HMGCS1, which are directly involved in the cholesterol mevalonate synthesis pathway. In contrast, both "low response lines", show increased expression of proteins involved in regulating the stability and recycling of lipoprotein receptor complexes, such as PCSK9, SCARB1, a cell surface HDL receptor that mediates HDL-cholesteryl ester uptake, as well as ApoE a plasma protein that participates in the transport of cholesterol and other lipids between cells and has been linked to the effect of statins (23)(24)(25)(26)(27)(28)(29)(30)(31). Lipoprotein receptor complexes play an important role in the regulation of plasma and intracellular cholesterol homeostasis (32).…”

Section: Linking Variable Responses To Protein Expression and Stoichi...mentioning

confidence: 99%

Screening for variable drug responses using human iPSC cohorts

Platani

Jiang

Davidson

et al. 2023

Preprint

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We have used a cohort of human induced pluripotent stem cell (hiPSC) lines to develop a laboratory-based drug screening platform to predict variable drug responses of potential clinical relevance. Our approach is based on the findings that hiPSC lines reflect the genetic identity of the donor and that pluripotent hiPSC lines express a broad repertoire of gene transcripts and proteins. We demonstrate that a cohort of hiPSC lines from different donors can be screened efficiently in their pluripotent state using high throughput cell painting assays, allowing detection of variable phenotypic responses to a wide range of clinically approved drugs, across multiple disease areas. Furthermore, we provide information on mechanisms of drug-cell interactions underlying the observed variable responses by using quantitative proteomic analysis to compare sets of hiPSC lines that had been stratified objectively using cell painting data. We propose that information derived from comparative drug screening using curated libraries of hiPSC lines can help to increase the success rate of drug development pipelines and improve the delivery of safe new drugs suitable for a broader ethnic and gender diversity within human populations.

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