Biomechanical assessment of remote and postinfarction scar remodeling following myocardial infarction

Abstract

The importance of collagen remodeling following myocardial infarction (MI) is extensively investigated, but little is known on the biomechanical impact of fibrillar collagen on left ventricle post-MI. We aim to identify the significant effects of the biomechanics of types I, III, and V collagen on physio-pathological changes of murine hearts leading to heart failure. Immediately post-MI, heart reduces its function (EF = 40.94 ± 2.12%) while sarcomeres’ dimensions are unchanged. Strikingly, as determined by immunohistochemistry staining, type V collagen fraction significantly grows in remote and scar for sustaining de novo-types I and III collagen fibers’ assembly while hindering their enzymatic degradation. Thereafter, the compensatory heart function (EF = 63.04 ± 3.16%) associates with steady development of types I and III collagen in a stiff remote (12.79 ± 1.09 MPa) and scar (22.40 ± 1.08 MPa). In remote, the soft de novo-type III collagen uncoils preventing further expansion of elongated sarcomeres (2.7 ± 0.3 mm). Once the compensatory mechanisms are surpassed, the increased turnover of stiff type I collagen (>50%) lead to a pseudo-stable biomechanical regime of the heart (≅9 MPa) with reduced EF (50.55 ± 3.25%). These end-characteristics represent the common scenario evidenced in patients suffering from heart failure after MI. Our pre-clinical data advances the understanding of the cause of heart failure induced in patients with extended MI.

Human engineered heart tissue transplantation in a guinea pig chronic injury model

“…Yet, in the subacute setting, scars are not fully matured 24,25 . Over time collagen deposition increases 26 and fibroblasts undergo morphological adaptations (e.g. alignment) and change in gene expression towards a tendonlike state occurs 25 .…”

Attenuation corrected‐optical coherence tomography for quantitative assessment of skin wound healing and scar morphology

“…This morphological similarity between skin and physiological (normal) scar at the steady‐state stage (OCT reflectivity plateau) suggests a “stopping‐point” in further matrix accumulation. The correlation of scar morphology to tissue mechanical properties can also help computational modeling [69, 78] and characterization of pathological scars [79, 80] with in vivo information.…”

Engineering the Cellular Microenvironment of Post-infarct Myocardium on a Chip

“…After myocardial infarction, local elastic modulus in the infarcted region increases to 20–100 kPa due to scar formation and fibrosis ( 89 – 92 ). Rat models with coronary artery ligation demonstrate myocardial stiffening over time, with elastic modulus increasing from 18 to 55 kPa ( 90 ), and increased stiffness has been observed in the infarct zone as early as 1 day post-infarction ( 93 ). In addition to temporal changes, regional stiffness varies between the infarct zone, border zone, and remote zone by 3 days post-infarction ( 94 ).…”

“…Elastic modulus progressively decreases in the border zone at a rate of 8.5 kPa/mm toward remote tissue ( 90 ). Because investigating the effects of tissue stiffness with in vivo models is confounded by many other concurrent changes, including matrix composition ( 93 ), in vitro models have been implemented to elucidate the effects of stiffness and other aspects of fibrosis on cardiac cell phenotypes. In this section, we will describe 2-D and 3-D in vitro models of cardiac fibrosis that focus primarily on recapitulating uniform or spatiotemporal changes in stiffness.…”