Atherosclerotic Plaque Rupture in Humans and Mice

Jacques Ohayon, PhD

Laboratory TIMC-IMAG/DyCTiM, UJF, CNRS UMR 5525, In3S
Faculty of Medicine  of Grenoble - 38706 La Tronche Cedex, France

Elucidating atherosclertic vulnerable plaque rupture by modeling cross substitution of ApoE-/- mouse and human plaque component stiffnesses - Biomechanics and Modeling in Mechanobiology. (in press), 2011 - The structure of mouse atherosclerotic lesions may differ from that of humans, and mouse atherosclerotic plaque do not rupture except in some specific locations such as the brachiocephalic artery. Recently, our group was the first to observe that the amplitudes of in vivo stresses in ApoE-/- mouse aortic atherosclerotic lesions were much lower and differed from those found in a previous work performed on human lesions. In this previous preliminary work, we hypothesized that the plaque mechanical properties (MP) may in turn be responsible for such species differences. However, the limited number of human samples used in our previous comparative study was relevant but not sufficient to broadly validate such hypothesis. Therefore, in this study, we propose an original finite element strategy that reconstructs the in vivo stress/strain (IVS/S) distributions in ApoE-/- artherosclerotic vessel based on cross substitution of ApoE-/- mouse and human plaque components stiffnesses and including residual stress/strain (RS/S). Our results: 1) showed that including RS/S decreases by a factor 2 the amplitude of maximal IVS/S, and more importantly 2) demonstrated that the MP of the ApoE-/- plaque constituents are mainly responsible for the low level - compared to human - of intraplaque stress in ApoE-/- mouse aortic atherosclerotic lesions (8.362.63 kPa versus 182.2555.88 kPa for human). Our study highlights that such differences in the distribution and amplitude of vessel wall stress might be one key feature for explaining for the difference in lesion stability between human coronary and mouse aortic lesions.







Fig. 1: Influence of the mechanical properties (MP) of the atherosclerotic vessel on the in vivo stress distributions. Finite-Element (FE) simulations were performed for 3 atherosclerotic mouse lesions. Column a: Zero-stress configurations of pathological samples # 3, 4 and 2 for mice of 20, 25 and 30 weeks, respectively (yellow: LiRi regions, orange: CeFb regions, red: HyFb regions, white: arterial wall). Column b) In vivo stress distributions computed by considering the mouse MP. Column c) In vivo stress distributions computed by considering the human MP. A pressure of 14.5 kPa was used for these FE simulations. Red arrows indicate regions with higher stresses.

Selected Publications

  Ohayon J, Mesnier N, Broisat A, Toczek J, Riou L, Tracqui P. Elucidating atherosclertic vulnerable plaque rupture by modeling cross substitution of ApoE-/- mouse and human plaque component stiffnesses. Biomechanics and Modeling in Mechanobiology. (in press), 2011.


•  Ohayon J, Gharib AM, Garcia A, Heroux J, Yazdani SK, Malvè M, Tracqui P, Martinez MA, Doblare M, Finet G, Pettigrew RI. Is arterial wall-strain stiffening and additional process responsible for atherosclerosis in coronary bifurcations? in vivo Study Based on Dynamic CT and MRI. Am J Physiol Heart Circ Physiol. 301(3):H1097-106, 2011.


 Broisat A, Toczek J, Mesnier N, Tracqui P, Ghezzi C, Ohayon J, Riou L. Assessing the low levels of mechanical stress in aortic atherosclerosis lesions from ApoE-/-mouse . Arterioscler Thromb Vasc Biol. 31(5):1007-10, 2011.


 Tracqui P, Broisat A, Toczek J, Mesnier N, Ohayon J, Riou L. Mapping elasticity moduli of atherosclerotic plaque in situ via atomic force microscopy . Journal of structural Biology 174(1):115-23, 2011.


  Heroux J, Gharib AM, Danthi NS, Cecchini S, Ohayon J, Pettigrew RI. High Affinity avb3 Integrin Targeted Optical Probe as a New Imaging Biomarker for Early Atherosclerosis: Initial Studies in Watanabe Rabbits. Mol Imaging Biol., 12(1):2-8, 2010.


•  Soloperto G, Keenan NG, Sheppard MN, Ohayon J, Wood N, Pennell DJ, Mohiaddin RH, Xu XY. A combined imaging, computational and histological analysis of a ruptured carotid plaque. Artery Research, 4(2):59-65, 2010.


  Le Floc'h S, Cloutier G, Finet G, Tracqui P, Pettigrew RI, Ohayon J. On the potential of a new IVUS elasticity modulus imaging approach for detecting vulnerable atherosclerotic coronary plaques: in vitro vessel phantom study. Phys. Med. Biol., 55:5701-5721, 2010.


  Finet G., Huo Y, Riouffol G, Ohayon J, Guerin P, Kassab GS.  Structure-function relation in the coronary artery tree: from fluid dynamics to arterial bifurcations. EuroIntervention, 6:J10-J15, 2010.


  Le Floc'h S, Ohayon J, Tracqui P, Finet G, Gharib AM, Maurice R, Cloutier G, Pettigrew RI. Vulnerable Atherosclerotic Plaque Elasticity Reconstruction Based on a Segmentation-Driven Optimization Procedure Using Strain Measurements: Theoretical Framework. IEEE Trans Med Imaging, 28(7):1126-37, 2009.


•  Kotys MS, Herzka DA, Vonken EJ, Ohayon J, Heroux J, Gharib AM, Stuber M, Pettigrew RI. Profile order and time-dependent artifacts in contrast-enhanced coronary MR angiography at 3T: origin and prevention. Magn Reson Med., 62(2):292-9, 2009.


  Eskandari H, Salcudean SE, Rohling R, Ohayon J. Viscoelastic characterization of soft tissue from dynamic finite element models. Physics in Medicine and Biology, 53(22):6569-90, 2008.


•  Ohayon J, Finet G, Gharib AM, Herzka DA, Tracqui P, Heroux J, Rioufol G, Kotys MS, Elagha A, Pettigrew RI. Necrotic core thickness asnd positive arterial remodeling index: emergent biomechanical factors for evaluating the risk of plaque rupture. Am J Physiol Heart Circ Physiol., 295(2):H717-27, 2008.


  Ohayon J, Dubreuil O, Tracqui P, Le Floc'h S, Rioufol G, Chalabreysse L, Thivolet F, Pettigrew RI, Finet G. Influence of residual stress/strain on the biomechanical stability of vulnerable coronary plaques: potential impact for evaluating the risk of plaque rupture. Am J Physiol Heart Circ Physiol., 293(3):H1987-96, 2007.


•  Boudou T., Ohayon J., Arntz Y., Finet G., Picart C., Tracqui P. An extended modeling of the micropipette aspiration experiment for the characterization of the Young’s modulus and Poisson’s ratio of adherent thin biological samples: Numerical and experimental studies. Journal of Biomechanics, 39:1677-85, 2006.


•  Boudou T., Ohayon J., Picart C., Tracqui P. Characterization of the Young’s modulus and Poisson’s ratio of polyacrylamide gels using micropipette aspiration technique. Biorheology, 43(6): 721-8, 2006.