Valvular & structural heart disease
Aortic Valve Stenosis Causes Accumulation of Extracellular Hemoglobin and Systemic Endothelial Dysfunction
Authors' conclusion
AS increases postvalvular swirling blood flow in the central ascending aorta, triggering RBC fragmentation with the accumulation of hemoglobin in the plasma. This increases NO consumption in blood, thereby limiting vascular NO bioavailability. Thus, AS itself promotes systemic endothelial dysfunction independent of other established risk factors.
Study context
- Population
- Mice with experimentally induced AS devoid of standard modifiable CV risk factors; patients with AS scheduled for TAVR
Methodological detailsexperimental mouse model, human cohorts
- Experimental mouse model
- Human cohorts
Main finding
As reported in the abstract
- Mice: induction of AS caused systemic endothelial dysfunction
- Mice: higher transvalvular gradient associated with elevated eryptosis, increased extracellular Hb and increased plasma nitric oxide (NO) consumption; Hb sequestration by haptoglobin restored endothelial function
- Patients: smaller aortic valve orifice area, higher postvalvular mechanical stress in central ascending aorta, associated with elevated extracellular Hb, red blood cell (RBC)-derived microvesicles, eryptotic cells, lower haptoglobin without clinically relevant anaemia, and endothelial dysfunction
- Transfer experiments: reducing extracellular Hb with haptoglobin or removing fluid dynamic stress by TAVR restored endothelial function
- Remaining circulating RBCs before and after TAVR had intact membrane function, deformability and resistance to osmotic and hypoxic stress
Original publication
Aortic Valve Stenosis Causes Accumulation of Extracellular Hemoglobin and Systemic Endothelial Dysfunction. Circulation. Published 5 June 2024. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →