Fibrosis after Myocardial Infarction: An Overview on Cellular Processes, Molecular Pathways, Clinical Evaluation and Prognostic Value

Abstract

The ischemic injury caused by myocardial infarction activates a complex healing process wherein a powerful inflammatory response and a reparative phase follow and balance each other. An intricate network of mediators finely orchestrate a large variety of cellular subtypes throughout molecular signaling pathways that determine the intensity and duration of each phase. At the end of this process, the necrotic tissue is replaced with a fibrotic scar whose quality strictly depends on the delicate balance resulting from the interaction between multiple actors involved in fibrogenesis. An inflammatory or reparative dysregulation, both in term of excess and deficiency, may cause ventricular dysfunction and life-threatening arrhythmias that heavily affect clinical outcome. This review discusses cellular process and molecular signaling pathways that determine fibrosis and the imaging technique that can characterize the clinical impact of this process in-vivo.

Keywords: cardiac magnetic resonance; fibrosis; inflammation; molecular pathways; myocardial infarction; prognostic value.

Figure 1

Different phases of the healing process after myocardial infarction.

Figure 2

WNT/ β catenin pathway and its relation to gene transcription driving fibrogenesis. APC: Adenomatous polyposis coli protein; CK1α: Casein kinase 1α; DVL: Dishevelled protein; GSK3 β: Glycogen synthase kinase 3 β; LRP: Lipoprotein receptor-related proteins; P: phosphorus; SMAD: small mother against decapentaplegic protein; TGFβ: tumor growth factor β; YAP: yes-associated protein.

Figure 3

Description of the main patterns of myocardial fibrosis and the corresponding cardiac magnetic resonance images. Right panel: replacement fibrosis occurs in response to cardiomyocyte loss and can be observed in LGE image as a regional subendocardial scar (white arrows). Left panel: reactive fibrosis occurs without cardiomyocyte loss and can be observed in native T1 mapping image as raised native T1 values (1000–1200 ms).