Genetics: Implications for Prevention and Management of Coronary Artery Disease

Assimes, Themistocles L.; Roberts, Robert

doi:10.1016/j.jacc.2016.10.039

Cited by 97 publications

(56 citation statements)

References 170 publications

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“…Likewise, cardiac regeneration has the therapeutic potential to prevent the development of post-ischaemic heart failure 5 . The lack of successful translation of promising therapeutic strategies to the clinical arena includes several factors such as the use of hypothesis-driven, biased target discovery 6 , 7 and neglecting the interfering effects of common cardiovascular risk factors and their routine medications with cardioprotective pathways 4 , 8 . Therefore, for successful development of cardioprotective therapies for acute myocardial ischaemia/reperfusion injury and ischaemic heart failure, new ways to discover valid targets must be used.…”

Section: Introductionmentioning

confidence: 99%

Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischaemic heart? Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart

Perrino

Barabási

Condorelli

et al. 2017

Cardiovascular Research

106

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Despite advances in myocardial reperfusion therapies, acute myocardial ischaemia/reperfusion injury and consequent ischaemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischaemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signalling networks activated in the ischaemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets. High-throughput techniques allow high-resolution, genome-wide investigation of genetic variants, epigenetic modifications, and associated gene expression profiles. Platforms such as proteomics and metabolomics (not described here in detail) also offer simultaneous readouts of hundreds of proteins and metabolites. Isolated omics analyses usually provide Big Data requiring large data storage, advanced computational resources and complex bioinformatics tools. The possibility of integrating different omics approaches gives new hope to better understand the molecular circuitry activated by myocardial ischaemia, putting it in the context of the human ‘diseasome’. Since modifications of cardiac gene expression have been consistently linked to pathophysiology of the ischaemic heart, the integration of epigenomic and transcriptomic data seems a promising approach to identify crucial disease networks. Thus, the scope of this Position Paper will be to highlight potentials and limitations of these approaches, and to provide recommendations to optimize the search for novel diagnostic or therapeutic targets for acute ischaemia/reperfusion injury and ischaemic heart failure in the post-genomic era.

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Section: Introductionmentioning

confidence: 99%

Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischaemic heart? Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart

Perrino

Barabási

Condorelli

et al. 2017

Cardiovascular Research

106

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“…The family-based approach of the TCGS enables the study to take a flexible approach to gene discovery, encompassing association and linkage approaches, and gives the potential to study aspects such as heritability of disease-related traits and parent-of-origin effects. The combination of linkage and association approaches has proven very effective in studies of various diseases/disease traits [21]. …”

Section: Discussionmentioning

confidence: 99%

Rationale and Design of a Genetic Study on Cardiometabolic Risk Factors: Protocol for the Tehran Cardiometabolic Genetic Study (TCGS)

Sedaghati-Khayat

et al. 2017

JMIR Res Protoc

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BackgroundCardiometabolic risk factors comprise cardiovascular diseases and/or diabetes, and need to be evaluated in different fields.ObjectiveThe primary aim of the Tehran Cardiometabolic Genetic Study (TCGS) is to create a comprehensive genome-wide database of at least 16,000 Tehranians, who are participants of the ongoing Tehran Lipid and Glucose Study (TLGS) cohort.MethodsTCGS was designed in collaboration with the Research Institute for Endocrine Sciences and the genetic company deCODE. Participants had already been followed for over a 20-year period for major cardiometabolic-related health events including myocardial infarction, stroke, diabetes mellitus, hypertension, obesity, hyperlipidemia, and familial hypercholesterolemia.ResultsThe TCGS cohort described here comprises 17,186 (86.3%) of the 19,905 TLGS participants who provided a baseline blood sample that was adequate for plasma and deoxyribonucleic acid analysis. This study is comprised of 849 individuals and 3109 families with at least one member having genotype information. Finally, 5977 males and 7422 females with the total genotyping rate of 0.9854 were genotyped with HumanOmniExpress-24-v1-0 bead chips (containing 649,932 single-nucleotide polymorphism loci with an average mean distance of 4 kilobases).ConclusionsInvestigations conducted within the TCGS will seek to identify relevant patterns of genetic polymorphisms that could be related to cardiometabolic risk factors in participants from Tehran. By linking genome-wide data to the existing databank of TLGS participants, which includes comprehensive behavioral, biochemical, and clinical data on each participant since cohort inception in 1999, the TCGS will also allow exploration of gene-gene and gene-environment interactions as they relate to disease status.

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“…The GWAS approach is not able to recognize and explain the pathological changes and clinical progression of CAD phenotypes [21]. To extract more information in order to evaluate the heritability of CAD by both common and rare variants and to assess more accurately the clinical utility of genetic risk scores, very large sample sizes in mega-biobanks of at least half a million participants are needed [52]. Atherosclerotic process is a complex phenomenon involving epigenetic adjustments which are adapted and programmed to various gene expressions.…”

Section: Repercussions To Clinical Cardiologymentioning

confidence: 99%

Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases

Louridas

Lourida

2017

Healthcare

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Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

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Genetics: Implications for Prevention and Management of Coronary Artery Disease

Cited by 97 publications

References 170 publications

Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischaemic heart? Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart

Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischaemic heart? Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart

Rationale and Design of a Genetic Study on Cardiometabolic Risk Factors: Protocol for the Tehran Cardiometabolic Genetic Study (TCGS)

Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases

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