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Leopold, J. A., & Loscalzo, J. (2018). The Emerging Role of Precision Medicine in Cardiovascular Disease. Circ. Res. 122(9), 1302. Added by: Dr. Enrique Feoli (01/02/2021, 22:03) Last edited by: Dr. Enrique Feoli (10/02/2021, 01:30) |
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| Resource type: Journal Article DOI: 10.1161/CIRCRESAHA.117.310782 BibTeX citation key: Leopold2018 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Network Medicine Creators: Leopold, Loscalzo Collection: Circ. Res. |
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| Abstract |
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Precision medicine is an integrative approach to cardiovascular disease prevention and treatment that considers an individual’s genetics, lifestyle, and exposures as determinants of their cardiovascular health and disease phenotypes. This focus overcomes the limitations of reductionism in medicine, which presumes that all patients with the same signs of disease share a common pathophenotype and, therefore, should be treated similarly. Precision medicine incorporates standard clinical and health record data with advanced panomics (i.e., genomics, transcriptomics, epigenomics, proteomics, metabolomics, microbiomics) for deep phenotyping. These phenotypic data can then be analyzed within the framework of molecular interaction (interactome) networks to uncover previously unrecognized disease phenotypes, relationships between diseases, and select pharmacotherapeutics or identify potential protein-drug or drug-drug interactions. In this review, we discuss the current spectrum of cardiovascular health and disease, population averages and the response of extreme phenotypes to interventions, and population-based versus high-risk treatment strategies as a pretext to understanding a precision medicine approach to cardiovascular disease prevention and therapeutic interventions. We also consider the search for resilience and Mendelian disease genes, and argue against the theory of a single causal gene/gene product as a mediator of the cardiovascular disease phenotype as well as an Erlichian ‘magic bullet’ to solve cardiovascular disease. Finally we detail the importance of deep phenotyping and interactome networks, and the use of this information for rational polypharmacy. These topics highlight the urgent need for precise phenotyping to advance precision medicine as a strategy to improve cardiovascular health and prevent disease.
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| Notes |
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Network analysis has been used to examine endophenotypes and their overlapping relationships to different diseases. Inflammation, thrombosis, and fibrosis are endophenotypes that are linked pathologically and common to virtually all disease states, both in terms of response to injury and to repair 68–71. To explore biological and topological crosstalk between these endophenotypes, network analysis of the inflammasome, thrombosome, and fibrosome was undertaken. Mapping these networks to the human interactome identified inflammation, thrombosis, and fibrosis sub-regions that were highly overlapping and contained disease genes associated with complex diseases and cardiovascular risk factors. These sub-regions were found to be integral to the structure of the basic interactome network thereby highlighting the key role of these processes in (health and) disease 72.
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |