Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Telle, Å; Maleckar, MM; Wall, S; Powers, JD; Augustin, CM; Sundnes, J; Boyle, PM.
Mechanical Modeling of Cardiac Fibrosis with Explicit Spatial Representation of Cellular Structure and Collagen Alignment.
J Biomech Eng. 2025; 1-11
Doi: 10.1115/1.4070346
PubMed
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- Co-Autor*innen der Med Uni Graz
- Augustin Christoph
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- Abstract:
- Cardiac fibrosis is a pathological condition linked to various diseases, involving remodeling that impair the cardiac function. Common forms include replacement fibrosis, where damaged myocytes are substituted by collageneous tissue, and interstitial fibrosis, involving matrix expansion between individual myocytes. These occur alongside other remodeling processes, including myocardial stiffening and collagen alignment. However, the mechanical impact of each factor remains poorly understood. In this work, we used a computational model with explicit myocyte and collagen geometry to study the microscale mechanical effects of fibrotic remodeling. Replacement fibrosis was simulated by substituting half of the myocytes with extracellular matrix, while interstitial fibrosis was modeled by increasing transverse spacing. These geometric changes were combined with increased matrix and myocyte stiffness and collagen alignment to assess combined effects during contraction and stretch. Myocyte replacement led to substantially higher stresses during contraction (12.2 kPa vs. 5.0 kPa at baseline) and slightly reduced shortening (17% vs. 20%). Collagen alignment and myocyte stiffening mitigated increased stress levels. Stretch experiments showed that replacement fibrosis decreased fiber-direction stiffness, reducing tissue anisotropy. In contrast, interstitial expansion alone had minimal effect on contraction but, when combined with stiffening, proportionally increased tissue stiffness (doubling load values) during stretch while preserving tissue anisotropy. Our findings suggest that myocyte replacement leads to elevated stress in surviving myocytes, whereas interstitial fibrosis primarily contributes to tissue stiffening. Collagen alignment and myocyte stiffening may serve compensatory roles. Integrating microscale modeling with experimental data may offer deeper insights into the mechanical consequences of fibrotic remodeling.