Temporal and spatial changes in wall shear stress during atherosclerotic plaque progression in mice

Abstract

Wall shear stress (WSS) is involved in atherosclerotic plaque initiation, yet its role in plaque progression remains unclear. We aimed to study (i) the temporal and spatial changes in WSS over a growing plaque and (ii) the correlation between WSS and plaque composition, using animal-specific data in an atherosclerotic mouse model. Tapered casts were placed around the right common carotid arteries (RCCA) of ApoE−/− mice. At 5, 7 and 9 weeks after cast placement, RCCA geometry was reconstructed using contrast-enhanced micro-CT. Lumen narrowing was observed in all mice, indicating the progression of a lumen intruding plaque. Next, we determined the flow rate in the RCCA of each mouse using Doppler Ultrasound and computed WSS at all time points. Over time, as the plaque developed and further intruded into the lumen, absolute WSS significantly decreased. Finally at week 9, plaque composition was histologically characterized. The proximal part of the plaque was small and eccentric, exposed to relatively lower WSS. Close to the cast a larger and concentric plaque was present, exposed to relatively higher WSS. Lower WSS was significantly correlated to the accumulation of macrophages in the eccentric plaque. When pooling data of all animals, correlation between WSS and plaque composition was weak and no longer statistically significant. In conclusion, our data showed that in our mouse model absolute WSS strikingly decreased during disease progression, which was significantly correlated to plaque area and macrophage content. Besides, our study demonstrates the necessity to analyse individual animals and plaques when studying correlations between WSS and plaque composition.

Wall shear rates in human and mouse arteries: Standardization of hemodynamics for in vitro blood flow assays: Communication from the ISTH SSC subcommittee on biorheology

“…Several thrombosis studies using ferric chloride to injure mouse carotid arteries discuss the WSR value of 1300 to 1800 s −1 18 . In ApoE‐deficient mice with carotid arteries containing atherosclerotic plaques, a WSR on the order of 3500 to 4000 s −1 was found 19 . Also, in atherosclerotic human arteries, the WSR can rise considerably, up to 10 000 s −1 and higher 1 .…”

“…18 In ApoE-deficient mice with carotid arteries containing atherosclerotic plaques, a WSR on the order of 3500 to 4000 s −1 was found. 19 Also, in atherosclerotic human arteries, the WSR can rise considerably, up to 10 000 s −1 and higher. 1 In the The Complexity of Hemodynamics section we briefly touch upon these pathological WSRs and associated complex rheological conditions.…”

“…260--500 16 Carotid artery (ferric-chlorideinduced thrombosis) 300--500 17 1800--4000 [17][18][19]45 Coronary artery 2.6--5.0 13 100--350 13 Coronary artery (histology in ApoE Mesenteric arteries 0.41--0.66 26 170--330 26 Mesenteric arteries (laserinduced, ferric-chloride-induced) 80--150 27,28 1200--1700 27,28 Cremaster arteriole Cremaster arteriole (laser-induced) 40--60 30,31 700--1000 30,31…”

Carotid Wall Shear Rate as a Marker of Systemic Atherosclerosis and Atherosclerotic Cardiovascular Disease

“…было зафиксировано прогрессирующее снижение каротидного НСЭ и ССЭ после создания стеноза сонной артерии in vivo. Следует отметить, что НСЭ и ССЭ снижались в течение периода 9-недельного наблюдения, несмотря на то что степень стеноза оставалась неизменной [24]. В исследовании B. Zhang и соавт.…”

A Systematic Review for the Design of In Vitro Flow Studies of the Carotid Artery Bifurcation

“…47 Moreover, there is no clear conclusion about the relation between low and high WSS in plaque vulnerability. 8,30,70 Turbulent/disordered flow-based parameters are mostly reported by ultrasound and optical PIV studies. Some of these parameters clearly show and quantify regions of disordered flow, however some other quantitative parameters are hard to interpret.…”