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Mar 29, 2024
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In modern medical research, understanding the fundamental causes of cardiovascular events is crucial. This paper delves into new mechanisms of thrombosis formation, highlighting the key role of the gut microbial metabolite 2-methylbutyrylcarnitine (2MBC) in cardiovascular health. Thrombosis is the primary cause of severe cardiovascular events such as myocardial infarction, ischemic stroke, and pulmonary embolism. Based on the latest multi-omics integration methods and experimental models, this study provides profound insights into how 2MBC increases the risk of thrombosis.
Thrombosis is the main cause of death and disability resulting from adverse cardiovascular events, such as myocardial infarction, ischemic stroke, and pulmonary embolism. Elevated platelet reactivity is one of the important factors leading to thrombosis. Previous studies have shown that various diseases can cause high platelet reactivity, such as diabetes, obesity, hyperlipidemia, and so on. However, the mechanism of thrombosis remains unclear. On February 23, 2024, Cell Metabolism published online a research paper titled 'Gut microbial co-metabolite 2-methylbutyrylcarnitine exacerbates thrombosis via binding to and activating integrin α2β1'. This study used multi-omics integration, multiple in vivo thrombus models, and in vitro platelet function experiments to first discover and confirm that the abnormal accumulation of the gut microbiota-derived metabolite 2-methylbutyrylcarnitine (2MBC) is an important risk factor for elevated thrombosis risk. It can enhance platelet reactivity by directly binding to and activating the platelet membrane receptor integrin α2β1. This study provides new therapeutic targets and ideas for the prevention and treatment of thrombotic complications in metabolic diseases such as diabetes, obesity, and hyperlipidemia.
Metwarebio provided 16S rRNA gene Sequencing, Widely-Targeted Metabolomics, and Targeted Metabolomics detection services for this study.
The outbreak of COVID-19 has led to a sharp increase in thrombotic events, and studies on COVID-19 patients will help identify new mechanisms that contribute to the formation of thrombosis. Through metabolomics detection and analysis, the research team found that patients with COVID-19 had abnormally high levels of 2MBC in their feces, which was closely related to the risk of thrombosis. Subsequently, the team tested the plasma of patients infected with COVID-19 as well as patients with acute coronary syndrome or acute ischemic stroke, and found that the levels of 2MBC in these patients' plasma were significantly higher than those in healthy individuals. In summary, these findings suggest that the abnormal accumulation of 2MBC may be an important risk factor for high thrombotic risk. Furthermore, through various animal models, it has been verified that 2MBC can significantly accelerate thrombosis in vivo, which is related to platelet reactivity.
Through in vitro platelet function experiments, researchers confirmed the direct impact of 2MBC on platelets, including enhancing their aggregation, spreading, and contraction functions. Phosphoproteomics detection and analysis indicated that the integrin protein pathway may play a crucial role in this process. Through further screening and validation, the integrin family protein integrin α2β1 was identified as the key target mediating the promotion of high platelet reactivity by 2MBC. The researchers further confirmed that 2MBC can directly bind to and activate integrin α2β1 using experimental techniques such as computer-simulated docking and Biacore.
The researchers conducted experiments on mice by gavaging and intraperitoneally injecting 2MBA. The results showed that gavaging 2MBA could simulate the thrombogenic effect of 2MBC, while intraperitoneal injection had no significant effect. These results suggested that the intestinal flora might play a role in the formation of 2MBC. The researchers further confirmed that 2MBC is a metabolite produced by the intestinal flora, which can be converted from 2MBA under the action of intestinal bacteria through methods such as fasting/re-feeding, in vitro fecal bacteria fermentation, elimination of intestinal bacteria, and fecal transplantation. When the intestinal bacteria were eliminated beforehand, this process was blocked, and its thrombogenic effect disappeared accordingly. These results indicated that 2MBC may be a key intermediate substance linking intestinal flora dysfunction and high thrombotic risk.
The study's findings underscore the intricate relationship between gut microbiota and thrombosis, opening new doors for targeted prevention and treatment strategies in patients with metabolic diseases. As we continue to unravel the complexities of thrombosis, the importance of comprehensive metabolic profiling has never been clearer. MetwareBio, a leader in Metabolomics Detection Services, is at the forefront of this research, offering cutting-edge solutions to unravel metabolic pathways and identify therapeutic targets. For researchers and healthcare professionals seeking to advance their understanding of cardiovascular diseases and metabolic disorders, MetwareBio provides the essential tools and insights.
At Metwarebio lab in Boston we offer the following metabolomics analysis services to support your Cardiovascular disease research:
TM Widely-Targeted Metabolomics
Free Data Analysis Cloud platform with additional tools to support your research
