Novel Fibrillar and Non-Fibrillar Collagens Involved in Fibrotic Scar Formation after Myocardial Infarction

Author:

Ortega María1,Fábrega-García Maria Mar2,Molina-García Tamara1,Gavara Jose34ORCID,de Dios Elena4,Pérez-Solé Nerea14,Marcos-Garcés Víctor145ORCID,Padilla-Esquivel Jaime José6,Diaz Ana7,Martinez-Dolz Luis489,Jimenez-Navarro Manuel4101112,Rios-Navarro Cesar124ORCID,Bodí Vicente14513,Ruiz-Saurí Amparo124

Affiliation:

1. INCLIVA Biomedical Research Institute, 46100 Valencia, Spain

2. Department of Pathology, University of Valencia, 46010 Valencia, Spain

3. Centro de Biomateriales e Ingeniería Tisular, Universidad Politécnica de Valencia, 46022 Valencia, Spain

4. Centro de Investigación Biomédica en Red (CIBER)-CV, 28029 Madrid, Spain

5. Cardiology Department, Hospital Clínico Universitario, 46010 Valencia, Spain

6. Anatomic Pathology Department, Hospital Clínico Universitario, 46010 Valencia, Spain

7. Unidad Central de Investigación Médica, University of Valencia, 46010 Valencia, Spain

8. Cardiology Departament, Hospital Universitario Politécnico La Fe, 46026 Valencia, Spain

9. Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain

10. Servicio de Cardiología y Cirugía Cardiovascular-Área del Corazón, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain

11. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA Plataforma BIONAND), 29590 Málaga, Spain

12. Departamento de Medicina y Dermatología, Facultad de Medicina, Universidad de Málaga, 29010 Málaga, Spain

13. Department of Medicine, University of Valencia, 46010 Valencia, Spain

Abstract

Following myocardial infarction (MI), adverse remodeling depends on the proper formation of fibrotic scars, composed of type I and III collagen. Our objective was to pinpoint the participation of previously unreported collagens in post-infarction cardiac fibrosis. Gene (qRT-PCR) and protein (immunohistochemistry followed by morphometric analysis) expression of fibrillar (types II and XI) and non-fibrillar (types VIII and XII) collagens were determined in RNA-sequencing data from 92 mice undergoing myocardial ischemia; mice submitted to permanent (non-reperfused MI, n = 8) or transient (reperfused MI, n = 8) coronary occlusion; and eight autopsies from chronic MI patients. In the RNA-sequencing analysis of mice undergoing myocardial ischemia, increased transcriptomic expression of collagen types II, VIII, XI, and XII was reported within the first week, a tendency that persisted 21 days afterwards. In reperfused and non-reperfused experimental MI models, their gene expression was heightened 21 days post-MI induction and positively correlated with infarct size. In chronic MI patients, immunohistochemistry analysis demonstrated their presence in fibrotic scars. Functional analysis indicated that these subunits probably confer tensile strength and ensure the cohesion of interstitial components. Our data reveal that novel collagens are present in the infarcted myocardium. These data could lay the groundwork for unraveling post-MI fibrotic scar composition, which could ultimately influence patient survivorship.

Funder

“Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER”

Conselleria de Educación—Generalitat Valenciana

Agencia Estatal de Investigación

Publisher

MDPI AG

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