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Long Noncoding RNAs—Biomarkers for High-Altitude-Induced Thrombosis and Beyond?Funding This study was supported by Ludwig Boltzmann Gesellschaft.
Long noncoding RNAs (lncRNAs), containing >200 nucleotides, together with microRNAs (miRNAs) belong to the large group of noncoding RNAs originally considered to be junk. However, evidence, accumulated over recent years, has assigned important regulatory roles to these types of RNAs in health and disease. Noncoding RNAs are involved in the development of cardiovascular diseases and pathological vascular processes such as vascular remodeling, vascular leakage, angiogenesis, formation of aneurysm, diabetic retinopathy, and atherosclerosis.   No such association had yet been described between these RNAs and deep vein thrombosis (DVT). In this issue of Thrombosis and Haemostasis, Jha and colleagues describe a link between particular noncoding RNAs and high-altitude induced DVT. High-altitude exposure is known to activate the coagulation system. By analyzing the expression profile of lncRNAs, Jha and colleagues show here that higher levels of the lncRNAs LINC00659 and UXT-AS1 are present in peripheral blood from patients suffering from high-altitude-induced DVT as compared with levels seen in high-altitude control subjects without DVT. They found that LINC00659 and UXT-AS1 acted as “sponges” by competing for miRNAs miR-15 and miR-143, which would otherwise inhibit the expression of the prothrombotic genes SERPINE1 and HIF1A. Thus, LINC00659 and UXT-AS1 indirectly regulate thrombosis. Interestingly HIF1A regulates the expression of the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain containing 3 (NLRP3) inflammasome which is involved in the development of venous thrombosis under hypoxia. On the other hand, SERPINE1, also known as plasminogen activator inhibitor 1, is an inhibitor of fibrinolysis that has long been known to be a risk factor for thrombosis and to be regulated by hypoxia.   Taken together, this study provides evidence for an association between a particular profile of lncRNAs expressed in peripheral blood and the risk to suffer from a thrombotic event after high-altitude exposure. Based on the data presented by Jha and colleagues, one could speculate that lncRNAs might hold the potential to be used as biomarkers to predict the risk for future thrombotic events in individual patients. Thus, investigations addressing this research question seem highly warranted.
Received: 13 August 2021
Accepted: 14 August 2021
16 August 2021 (online)
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