Assessing the low levels of mechanical stress in aortic atherosclerosis lesions from ApoE-/-mouse - Arterioscler Thromb Vasc Biol. 31(5):1007-10, 2011 - Despite the fact that mechanical stresses are well recognized as key determinants for atherosclerotic plaque rupture, very little is known about stress amplitude and distribution in atherosclerotic lesions, even in the standard apoE-/- mouse model of atherosclerosis. Our objectives were to combine immunohistology, atomic force microscopy (AFM) measurements and finite element computational analysis for the accurate quantification of stress amplitude and distribution in apoE-/- mouse aortic atherosclerotic lesions. Residual stresses and strains (RSS) were released by radially cutting aortic arch segments from 7- to 30 weeks-old pathological apoE-/- (n=25) and healthy control mice (n=20). Immunohistology, AFM, and biomechanical modelling taking into account regional RSS were performed. Maximum stress values were observed in the normal arterial wall (276 ± 71 kPa), whereas low values(<20kPa) were observed in all plaque areas. Stress distribution was not correlated to macrophage infiltration. Low mechanical stress amplitude was observed in apoE-/- mice aortic atherosclerotic lesions. This original study provides a basis for further investigations aimed at determining whether low stress levels are responsible for the apparently higher stability of murine aortic atherosclerotic lesions.
Fig. 1: Computation of the in vivo stress distributions in mouse atherosclerotic arterial wall submitted to physiological internal pressure of 14.5kPa and without considering residual stress/strain RS/S (columns b and c) or taking into account RS/S (columns d and e). Column a: close unloaded configurations of 3 atherosclerotic lesions (pathological samples # 4, 3 and 1 for mice of 20, 25 and 30 weeks, respectively). (yellow: LiRi regions, orange: CeFb regions, red: HyFb regions, white: arterial wall). Rectangular frames highlight intraplaque stress distributions only.
Fig. 2: Description of the protocol performed on human specimen I to obtain the geometry of the macroscopic zero-stress configuration. A) isolated left anterior descending coronary sample of 4mm length. B) zero-stress configuration obtained 3 hours after radial sectioning of the healthy arc. The opening angle was measured as 143°. C) macroscopic histological observation of the same sample enabling the contours of the plaque constituents to be defined. D) microscopic histological view of the thin fibrous cap, from which the cap thickness CTh was approximated (CTh close to 94 µm). LC= lipid core; CF: cellular fibrosis.
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