title: Thin-cap fibroatheroma rupture is associated with a fine interplay of shear and wall stress.
abstract: In this review, we summarized the effect of mechanical factors (shear and wall stress) on thin-cap fibroatheroma formation and rupture. To make this review understandable for a biology-oriented audience, we start with detailed definitions of relevant mechanical metrics. We then describe how biomechanics has supported histopathologic efforts to understand the basis of plaque rupture. In addition to plaque rupture, biomechanics also contributes toward the progression of thin-cap fibroatheroma through a multitude of reported mechanobiological mechanisms. We thus propose a new mechanism whereby both shear stress and wall stress interact to create thin-cap fibroatheromas. Specifically, when regions of certain blood flow and wall mechanical stimuli coincide, they synergistically create inflammation within the cellular environment that can lead to thin-cap fibroatheroma rupture. A consequence of this postulate is that local shear stress is not sufficient to cause rupture, but it must coincide with regions of local tissue stiffening and stress concentrations that can occur during plaque progression. Because such changes to the wall mechanics occur over a micrometer scale, high spatial resolution imaging techniques will be necessary to evaluate this hypothesis and ultimately predict plaque rupture in a clinical environment.
authors: From the Department of Bioengineering, Imperial College London, London, United Kingdom (R.M.P., S.M.B., V.V.M., R.K.); NHLI, Imperial College London and NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom (R.d.S.); and MRC-Clinical Sciences Centre, Imperial College London, London, United Kingdom (E.P.).
authors: Ryan M
authors: RM
authors: Pedrigi
authors: From the Department of Bioengineering, Imperial College London, London, United Kingdom (R.M.P., S.M.B., V.V.M., R.K.); NHLI, Imperial College London and NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom (R.d.S.); and MRC-Clinical Sciences Centre, Imperial College London, London, United Kingdom (E.P.).
authors: Ranil
authors: R
authors: de Silva
authors: From the Department of Bioengineering, Imperial College London, London, United Kingdom (R.M.P., S.M.B., V.V.M., R.K.); NHLI, Imperial College London and NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom (R.d.S.); and MRC-Clinical Sciences Centre, Imperial College London, London, United Kingdom (E.P.).
authors: Sandra M
authors: SM
authors: Bovens
authors: From the Department of Bioengineering, Imperial College London, London, United Kingdom (R.M.P., S.M.B., V.V.M., R.K.); NHLI, Imperial College London and NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom (R.d.S.); and MRC-Clinical Sciences Centre, Imperial College London, London, United Kingdom (E.P.).
authors: Vikram V
authors: VV
authors: Mehta
authors: From the Department of Bioengineering, Imperial College London, London, United Kingdom (R.M.P., S.M.B., V.V.M., R.K.); NHLI, Imperial College London and NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom (R.d.S.); and MRC-Clinical Sciences Centre, Imperial College London, London, United Kingdom (E.P.).
authors: Enrico
authors: E
authors: Petretto
authors: From the Department of Bioengineering, Imperial College London, London, United Kingdom (R.M.P., S.M.B., V.V.M., R.K.); NHLI, Imperial College London and NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom (R.d.S.); and MRC-Clinical Sciences Centre, Imperial College London, London, United Kingdom (E.P.). r.krams@imperial.ac.uk.
authors: Rob
authors: R
authors: Krams
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001696:Biomechanical Phenomena; D018450:Disease Progression; D005355:Fibrosis; D006801:Humans; D040542:Mechanotransduction, Cellular; D058226:Plaque, Atherosclerotic; D012039:Regional Blood Flow; D012307:Risk Factors; D012422:Rupture, Spontaneous; D013314:Stress, Mechanical
keywords: atherosclerosis; biomechanical phenomena; cellular mechanotransduction; genomics