Collagen XV preserves heart function and protects from pathological remodelling after myocardial infarction

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Increasing knowledge of the components involved in left ventricle (LV) remodelling and fibrotic processes after a myocardial infarction is crucial to understanding heart pathology. We have here analysed collagen XV (ColXV) expression in human myocardial infarct samples and assessed how its deficiency affects cardiac responses, such as fibrogenesis and tissue stiffness, after acute myocardial infarction (AMI) in mice. We first observed high ColXV expression in human infarction scars. After ligating the left anterior descending artery in mice, cardiac function and remodelling were monitored by echocardiography, elasticity assessment, immunohistochemical analysis and ultrastructural assessments. After AMI, Col15a1 −/− mice showed significantly increased tissue stiffness and upregulation of fibrosis‐related genes in the remote myocardium. Striking differences were observed between the genotypes in the scar ultrastructure, protein compositions, cardiomyocyte morphology and intracellular architecture. Furthermore, the proportion of immature collagen fibres in the infarct border zone increased in Col15a1 −/− mice, suggesting fragility and poor scar resistance to mechanical stress. Structural parameters indicated more substantial LV remodelling in the knockout mice, leading to a more dilated ventricle. Functionally, the ejection fraction and fractional shortening decreased significantly in Col15a1 −/− mice, indicating impaired heart contractile capacity. The results show that in the event of an AMI, ColXV plays an essential role in sustaining cardiac structure and function. In the absence of ColXV, dysregulated remodelling results in disrupted scar and infarct border zone, and stiffer left ventricle. These changes lead to a more severe cardiac phenotype and may affect long‐term survival after AMI.

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