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Published on: October 26, 2020
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Coagulation factor XII contributes to renin activation, heart failure progression, and mortality
Biorxiv : the Preprint Server for Biology
|September 24, 2024
Summary
Activated coagulation factor XII generates active renin, driving heart failure and mortality by overactivating the renin-angiotensin-aldosterone system (RAAS). This discovery offers new therapeutic targets for heart failure treatment.
Area of Science:
- Cardiovascular Medicine
- Hemostasis and Thrombosis
- Renal Physiology
Background:
- Symptomatic heart failure (sHF) involves cardiac dysfunction, edema, and mortality, often driven by the overactivation of the renin-angiotensin-aldosterone system (RAAS).
- Renin initiates the RAAS cascade, but the precise mechanisms of its activation in pathological conditions remain largely unknown.
Purpose of the Study:
- To elucidate the upstream mechanisms responsible for renin activation in the context of symptomatic heart failure.
- To identify novel therapeutic targets for modulating the RAAS in sHF and related conditions.
Main Methods:
- Investigated the role of coagulation factor XII in renin activation using relevant biological assays and models.
- Assessed the link between activated factor XII, renin activity, RAAS markers, and heart failure progression in experimental settings.
Main Results:
- Demonstrated that activated coagulation factor XII directly generates active renin in the circulation.
- Established a direct correlation between activated factor XII, pathological RAAS activation, and the development of sHF.
- Showcased the association of this pathway with increased mortality in sHF models.
Conclusions:
- Activated coagulation factor XII is a key upstream activator of renin, linking hemostasis to RAAS overactivation in sHF.
- This finding presents a novel therapeutic strategy for managing RAAS-driven symptomatic heart failure.
- Targeting the interaction between coagulation factor XII and renin may offer a new paradigm for treating sHF and other related pathologies.
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