Development and Implementation of an Integrated Preclinical Atherosclerosis Database.

Autor:	Xiang RR; Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (R.R.X., Y.W., B.V.C., I.Z.J.)., Wang Y; Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (R.R.X., Y.W., B.V.C., I.Z.J.)., Shuey MM; Division of Genetic Medicine (M.M.S., Q.S.W.), Vanderbilt University Medical Center, Nashville, TN., Carvajal BV; Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (R.R.X., Y.W., B.V.C., I.Z.J.)., Wells QS; Division of Genetic Medicine (M.M.S., Q.S.W.), Vanderbilt University Medical Center, Nashville, TN.; Department of Biomedical Informatics (Q.S.W.), Vanderbilt University Medical Center, Nashville, TN.; Division of Cardiovascular Medicine (Q.S.W., J.A.B.), Vanderbilt University Medical Center, Nashville, TN., Beckman JA; Division of Cardiovascular Medicine (Q.S.W., J.A.B.), Vanderbilt University Medical Center, Nashville, TN., Jaffe IZ; Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (R.R.X., Y.W., B.V.C., I.Z.J.).
Jazyk:	angličtina
Zdroj:	Circulation. Genomic and precision medicine [Circ Genom Precis Med] 2024 Apr; Vol. 17 (2), pp. e004397. Date of Electronic Publication: 2024 Apr 02.
DOI:	10.1161/CIRCGEN.123.004397
Abstrakt:	Background: Basic scientists have used preclinical animal models to explore mechanisms driving human diseases for decades, resulting in thousands of publications, each supporting causative inferences. Despite substantial advances in the mechanistic construct of disease, there has been limited translation from individual studies to advances in clinical care. An integrated approach to these individual studies has the potential to improve translational success. Methods: Using atherosclerosis as a test case, we extracted data from the 2 most common mouse models of atherosclerosis (ApoE [apolipoprotein E]-knockout and LDLR [low-density lipoprotein receptor]-knockout). We restricted analyses to manuscripts published in 2 well-established journals, Arteriosclerosis, Thrombosis, and Vascular Biology and Circulation , as of query in 2021. Predefined variables including experimental conditions, intervention, and outcomes were extracted from each publication to produce a preclinical atherosclerosis database. Results: Extracted data include animal sex, diet, intervention type, and distinct plaque pathologies (size, inflammation, and lipid content). Procedures are provided to standardize data extraction, attribute interventions to specific genes, and transform the database for use with available transcriptomics software. The database integrates hundreds of genes, each directly tested in vivo for causation in a murine atherosclerosis model. The database is provided to allow the research community to perform integrated analyses that reflect the global impact of decades of atherosclerosis investigation. Conclusions: This database is provided as a resource for future interrogation of sub-data sets associated with distinct plaque pathologies, cell type, or sex. We also provide the methods and software needed to expand this data set and apply this approach to the extensive repository of peer-reviewed data utilizing preclinical models to interrogate mechanisms of diverse human diseases. Competing Interests: Disclosures Dr Beckman has consulted for Janssen, JanOne, and Novartis and received grant funding from Bristol Myers Squibb. Dr Jaffe has consulted for Boehringer Ingelheim. The other authors report no conflicts.
Databáze:	MEDLINE
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