Mevalonic acid exerts procoagulant effect by potentiating factor Xa

doi:10.1007/s13659-025-00564-1

Natural Products and Bioprospecting ›› 2026, Vol. 16 ›› Issue (1): 11-11.DOI: 10.1007/s13659-025-00564-1

• Original Article • Previous Articles Next Articles

Mevalonic acid exerts procoagulant effect by potentiating factor Xa

Liyuan Niu¹, Chuanfeng Liu², Shaoying Wang³, Qikai Yin³, Shiping Lin³, Musan Yan³, Wenshuo Li³, Yuanjie Yin³, Wei Wang², Wenjuan Yu⁴, Xiaopeng Tang^3,5, Min Xue³, Yuewei Wang¹

1. Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong, China;
2. Department of Hematology, Affiliated Hospital of Qingdao University, Qingdao 266003, China;
3. School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong, China;
4. Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China;
5. Shandong Key Laboratory of Pathogenesis and Prevention of Brain Diseases, Qingdao 266071, Shandong, China

Received:2025-06-15 Online:2026-03-25 Published:2026-02-14
Contact: Xiaopeng Tang,E-mail:tangxiaopeng@qdu.edu.cn;Min Xue,E-mail:xuemin@qdu.edu.cn;Yuewei Wang,E-mail:wangyw791128@hotmail.com
Supported by:
Taishan Scholars Program for Young Experts of Shandong Province, tsqn202312177, Xiaopeng Tang, the National Science Foundation of China, 32371162, Xiaopeng Tang, Shandong Provincial Natural Science Foundation, ZR2025ZD03, Xiaopeng Tang, Shandong Provincial Natural Science Foundation, ZR2024QH554, Min Xue, Shandong Postdoctoral Science Foundation, SDCX-ZG-202400149, Shaoying Wang, Start-up funding from Qingdao University, DC2300000302, Xiaopeng Tang.

Mevalonic acid exerts procoagulant effect by potentiating factor Xa

Liyuan Niu¹, Chuanfeng Liu², Shaoying Wang³, Qikai Yin³, Shiping Lin³, Musan Yan³, Wenshuo Li³, Yuanjie Yin³, Wei Wang², Wenjuan Yu⁴, Xiaopeng Tang^3,5, Min Xue³, Yuewei Wang¹

1. Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong, China;
2. Department of Hematology, Affiliated Hospital of Qingdao University, Qingdao 266003, China;
3. School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong, China;
4. Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China;
5. Shandong Key Laboratory of Pathogenesis and Prevention of Brain Diseases, Qingdao 266071, Shandong, China

通讯作者: Xiaopeng Tang,E-mail:tangxiaopeng@qdu.edu.cn;Min Xue,E-mail:xuemin@qdu.edu.cn;Yuewei Wang,E-mail:wangyw791128@hotmail.com
基金资助:
Taishan Scholars Program for Young Experts of Shandong Province, tsqn202312177, Xiaopeng Tang, the National Science Foundation of China, 32371162, Xiaopeng Tang, Shandong Provincial Natural Science Foundation, ZR2025ZD03, Xiaopeng Tang, Shandong Provincial Natural Science Foundation, ZR2024QH554, Min Xue, Shandong Postdoctoral Science Foundation, SDCX-ZG-202400149, Shaoying Wang, Start-up funding from Qingdao University, DC2300000302, Xiaopeng Tang.

Abstract

Abstract: Thrombosis pathogenesis is closely linked to dysregulated lipid metabolism and inflammatory processes. However, the direct regulatory role of mevalonate pathway within the coagulation cascade is still not well understood. This study aimed to elucidate the regulatory effects of mevalonic acid (MVA) on the coagulation system. The effects of MVA on coagulation were measured by recalcification. Enzymatic kinetic analysis and natural substrate hydrolysis assays were performed to identify the coagulation target of MVA. Mice bleeding and thrombosis models were applied to evaluate the effects of MVA administration on hemostasis and thrombosis. Our current study reveals that MVA significantly accelerates plasma coagulation through potentiating the procoagulant activity of FXa, without influencing the platelet aggregation. Studies showed that MVA administration substantially shortened activated partial thromboplastin time, prothrombin time, and reduced bleeding time in both tail bleeding and saphenous vein injury models. Furthermore, using ferric chloride-induced thrombosis, deep vein thrombosis and cerebral infarction models, we observed that MVA markedly potentiated thrombus formation and stroke. Our findings establish for the first time that MVA directly regulates FXa procoagulant activity, while also suggesting potential crosstalk between lipid metabolic pathways and inflammatory signaling in coagulation modulation. These results provide novel mechanistic insights into coagulation abnormalities associated with metabolic disorders such as atherosclerosis and diabetes, highlighting the mevalonate pathway as a potential therapeutic target for thrombotic complications.

Key words: Mevalonic acid, FXa, Inflammation, Thrombosis, Metabolic disorders

摘要： Thrombosis pathogenesis is closely linked to dysregulated lipid metabolism and inflammatory processes. However, the direct regulatory role of mevalonate pathway within the coagulation cascade is still not well understood. This study aimed to elucidate the regulatory effects of mevalonic acid (MVA) on the coagulation system. The effects of MVA on coagulation were measured by recalcification. Enzymatic kinetic analysis and natural substrate hydrolysis assays were performed to identify the coagulation target of MVA. Mice bleeding and thrombosis models were applied to evaluate the effects of MVA administration on hemostasis and thrombosis. Our current study reveals that MVA significantly accelerates plasma coagulation through potentiating the procoagulant activity of FXa, without influencing the platelet aggregation. Studies showed that MVA administration substantially shortened activated partial thromboplastin time, prothrombin time, and reduced bleeding time in both tail bleeding and saphenous vein injury models. Furthermore, using ferric chloride-induced thrombosis, deep vein thrombosis and cerebral infarction models, we observed that MVA markedly potentiated thrombus formation and stroke. Our findings establish for the first time that MVA directly regulates FXa procoagulant activity, while also suggesting potential crosstalk between lipid metabolic pathways and inflammatory signaling in coagulation modulation. These results provide novel mechanistic insights into coagulation abnormalities associated with metabolic disorders such as atherosclerosis and diabetes, highlighting the mevalonate pathway as a potential therapeutic target for thrombotic complications.

关键词: Mevalonic acid, FXa, Inflammation, Thrombosis, Metabolic disorders

Liyuan Niu, Chuanfeng Liu, Shaoying Wang, Qikai Yin, Shiping Lin, Musan Yan, Wenshuo Li, Yuanjie Yin, Wei Wang, Wenjuan Yu, Xiaopeng Tang, Min Xue, Yuewei Wang. Mevalonic acid exerts procoagulant effect by potentiating factor Xa[J]. Natural Products and Bioprospecting, 2026, 16(1): 11-11.

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Mevalonic acid exerts procoagulant effect by potentiating factor Xa

Mevalonic acid exerts procoagulant effect by potentiating factor Xa

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