Less-deformable erythrocyte subpopulations biomechanically induce endothelial inflammation in sickle cell disease.

ABSTRACT:

Abstract

Sickle cell disease (SCD) is canonically characterized by reduced red blood cell (RBC) deformability, leading to microvascular obstruction and inflammation. Although the biophysical properties of sickle RBCs are known to influence SCD vasculopathy, the contribution of poor RBC deformability to endothelial dysfunction has yet to be fully explored. Leveraging interrelated in vitro and in silico approaches, we introduce a new paradigm of SCD vasculopathy in which poorly deformable sickle RBCs directly cause endothelial dysfunction via mechanotransduction, during which endothelial cells sense and pathophysiologically respond to aberrant physical forces independently of microvascular obstruction, adhesion, or hemolysis. We demonstrate that perfusion of sickle RBCs or pharmacolo

SUBMITTER: Caruso C 

PROVIDER: S-EPMC11561591 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature