Abstract 625: Low Endothelial Shear Stress Promotes the Differentiation of Early Atherosclerotic Lesions to Thin Cap Fibroatheromas
Objectives: Although atherosclerotic lesions develop in areas of low endothelial shear stress (ESS), the differentiaton of these lesions to thin cap fibroatheromas (TCFAs) has not been studied. We evaluated the hypothesis that arterial subsegments with very low ESS are those regions where early lesions become inflamed, acquire a fibrous cap and differentiate to TCFAs.
Methods: In 11 diabetic hyperlipidemic swine, IVUS-based geometrically correct 3D reconstruction of the coronary arteries was performed at baseline (wk 23) and follow up (wk 30). Baseline ESS was calculated using computational fluid dynamics, and minimally diseased subsegments of interest of 3 mm length were identified (n=142). Coronary arteries (n=31) were harvested at follow up and the subsegments of interest were stained histologically. Intima/media ratio, minimum fibrous cap thickness, lipid deposition (oil red O) and inflammation (CD45) were quantified. Atherosclerotic lesions were histopathologically classified into atheromas without evidence of fibrous cap (non-FCs, n=82) and TCFAs (n=60).
Results: TCFAs developed in subsegments with lower ESS as compared to non-FCs (0.9 vs. 1.2 Pa, p<0.01). Very low ESS (<0.5 Pa) was significantly associated with larger plaque size, increased lipid deposition, inflammatory cell infiltration (Fig A⇓) and fibrous cap thinning (Fig B⇓).
Conclusion: Subsegments with the lowest ESS are those regions where early lesions acquire fibrous cap, high-risk characteristics and differentiate to TCFAs. These findings suggest a basis for the identification of early lesions and stratification of their risk to evolve to TCFAs responsible for acute coronary syndromes.