期刊
SCANDINAVIAN CARDIOVASCULAR JOURNAL
卷 53, 期 1, 页码 1-8出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14017431.2019.1581943
关键词
Nitric oxide; arterial thrombosis; endothelial dysfunction; DNA variations; epigenetic modifications; personalized therapy; network medicine
资金
- Italian Ministry of Health [RRC-2015-2360454]
Objectives. Nitric oxide (NO) represents the most powerful endogenous molecule with vasodilator action mainly produced by endothelial nitric oxide synthase (eNOS) enzyme. Polymorphisms and epigenetic-sensitive mechanisms can modulate the expression of eNOS gene, leading to the endothelial dysfunction. This review updates on the mechanistic role of NO in the regulation of platelet activation, as well as the impact of eNOS genetic and epigenetic modifications on arterial thrombosis onset. Design. A systematic search was addressed to examination of PubMed databases with the following terms: nitric oxide; arterial thrombosis; endothelial dysfunction; DNA variations; epigenetic modifications; personalized therapy; network medicine. Results. G894T, -786T/C, and 4b/4a variable number tandem repeat (VNTR), are the main classes of polymorphisms harbored in eNOS gene associated to increased arterial thrombosis risk. DNA methylation, histone/non-histone modifications, and microRNA (miRNAs) can modulate eNOS gene expression. Investigators largely focused on the role of miRNAs in modulating NO production in arterial thrombosis development. In detail, miR-195, and miR-582 are inversely correlated both to eNOS and NO levels, thus suggesting novel biomarkers. Conclusion. We are far from incorporating omics pathogenic data from bench to arterial thrombosis bedside. Network medicine is an emerging paradigm that ideally overcomes the current shortcomings of the reductionist approach. Despite several clinical limitations, the network-based analysis of the interactome might reveal the key nodes underlying the perturbations of the arterial thrombosis, thus advancing personalized therapy.
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