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Published on: September 9, 2012
The foundation for investigating factor XI as a target for inhibition in human cardiovascular disease
Ahmed E Ali1, Richard C Becker2
1Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Insights
Investigating coagulation factor XI offers a potential therapeutic target for cardiovascular diseases like atrial fibrillation and stroke. Targeting factor XI may provide a safe and effective approach to managing thrombosis and inflammation.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Pharmacology
Background:
- Anticoagulant therapy is crucial for managing thrombosis in cardiovascular diseases such as acute coronary syndrome, chronic coronary syndrome, ischemic stroke, and atrial fibrillation.
- These conditions share underlying mechanisms including inflammation, endothelial dysfunction, oxidative stress, and immune dysregulation.
- The complexity of cardiovascular disease necessitates identifying common pathways for effective pharmacological intervention.
Purpose of the Study:
- To explore coagulation factor XI as a potential therapeutic target for cardiovascular diseases.
- To review the fundamental biochemistry and biological activity of factor XI in thrombosis, inflammation, and angiogenesis.
- To discuss novel drugs targeting factor XI and their clinical application.
Main Methods:
- Review of fundamental biochemistry of coagulation factor XI.
- Analysis of factor XI's role in thrombosis, inflammation, and angiogenesis.
- Summary of emerging factor XI-targeting drugs and clinical trial management strategies.
Main Results:
- Factor XI's central role in the coagulation cascade and its involvement in inflammatory processes.
- Identification of factor XI as a potential "sweet spot" for pharmacological intervention.
- Emergence of novel drugs targeting factor XI for therapeutic use.
Conclusions:
- Coagulation factor XI presents a promising target for treating thrombotic cardiovascular diseases.
- Targeting factor XI may offer a safe and effective alternative to current anticoagulants.
- Future research and clinical trials are essential to validate factor XI inhibition in patient care.
Abstract:
Anticoagulant therapy is a mainstay in the management of patients with cardiovascular disease and related conditions characterized by a heightened risk for thrombosis. Acute coronary syndrome, chronic coronary syndrome, ischemic stroke, and atrial fibrillation are the most common. In addition to their proclivity for thrombosis, each of these four conditions is also characterized by local and systemic inflammation, endothelial/endocardial injury and dysfunction, oxidative stress, impaired tissue-level reparative capabilities, and immune dysregulation that plays a critical role in linking molecular events, environmental triggers, and phenotypic expressions. Knowing that cardiovascular disease and thrombosis are complex and dynamic, can the scientific community identify a common pathway or specific point of interface susceptible to pharmacological inhibition or alteration that is likely to be safe and effective? The contact factors of coagulation may represent the proverbial "sweet spot" and are worthy of investigation. The following review provides a summary of the fundamental biochemistry of factor XI, its biological activity in thrombosis, inflammation, and angiogenesis, new targeting drugs, and a pragmatic approach to managing hemostatic requirements in clinical trials and possibly day-to-day patient care in the future.
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