Cerebral arteries in mice with sickle cell disease are exposed to larger areas of low wall shear stress
Abstract
Sickle cell anemia (SCA) is the most severe form of sickle cell disease and causes increased stroke risk, even in children. Hemodynamic mechanisms underlying cerebral vasculopathy remain unclear. To test the hypothesis that SCA causes disturbed flow and increased regions of low wall shear stress (WSS) in cerebral arteries, we combined high-frequency ultrasound, micro-computed tomography, and computational fluid dynamics (CFD) using mice that are homozygous sickle (SS) and heterozygous trait (AS) at 4, 12, and 24 wk of age. At 12 wk, common carotid artery diameters were 12.4%-18.6% larger in SS mice (P P P 2) in cerebral arteries of SS mice, even in straight regions of the arteries at 12 and 24 wk. Our findings indicate that SCA reduces blood velocity and volumetric blood flow in the cerebral arteries while increasing endothelial exposure to pathological shear stress, providing a link between altered hemodynamics and arterial wall damage unique to sickle cell disease.NEW & NOTEWORTHY Sickle cell disease hemodynamics identifies: 1) stenoses and aneurysms along the lengths of carotid and cerebral arteries in sickle cell transgenic mouse model; 2) disturbed flow in the straight regions of the carotid and cerebral arteries; and 3) reduced blood flow and increased regions of low wall shear stress can predispose cerebral arteries to pathological and accelerated arterial damage and risk of strokes.
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