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.
Highlights
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
The mean EF % and FS % significantly decreased at day 1 post-MI corresponding to a reduced heart function (from 70.1 ± 4.8% to 42.1 ± 6.6% (p < 0.0001) and from 66.7 ± 13.2% to 28.3 ± 5.3% (p < 0.0001), respectively)
Www.nature.com/scientificreports the compensatory mechanism seemed to re-establish the heart function during healing after MI, without any therapeutical intervention the end- outcome progressed towards a heart failure
Summary
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. An increase of total collagen expression associates with increased left ventricle stiffness[32], no functional consequence can be drawn regarding the causative effect of fibrillar collagen subtypes during the course of myocardial remodeling[9,10,11]. Correlative models relating the spatial distribution of collagen composition post-MI and the effect of biomechanical characteristics of collagen fibers on regional tissue remodelling are yet to be envisaged. Based on this background, the present study focuses for the first time on the causative role of biomechanical characteristics of types I, III, and V collagen on patho-physiological conditions of the heart within the healing processes after MI. We do anticipate that our scientific report will contribute to delineating the critical molecular and biomechanical regulators of infarcted heart undergoing temporal remodelling; bringing valuable knowledge and expanding the state of the art on tissue formation and remodeling such as remote and scar in other fields
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