Table 2.
Overview of key functions, conditions, analytical methods and biomarkers in different forms of fibrosis
| Type of fibrosis | Function | Disease conditions | Methods to detect in tissue | Blood biomarkers |
|---|---|---|---|---|
| Reparative fibrosis | Replacing necrotic cells | Myocyte necrosis (ischaemia, infection, autoimmunity, toxicity, gene mutations) |
Histochemistry (Sirius red and Azan blue) Cardiac MRI, late enhancement |
CITP, PICP PINP, PIIINP |
| Reactive fibrosis | New matrix production in between cells | Matrix production in response to an acquired or genetic trigger, such as stretch |
Histochemistry Cardiac MRI, T1 mapping of extracellular volume |
CITP, PICP, Galectin‐3, sST2, and periostin |
| Perivascular fibrosis | New matrix produced around vessels | Perivascular fibrosis upon pressure overload or vascular stress | Histochemistry | Unknown |
| Cells involved | ||||
| (Myo)fibroblasts | Reparative and reactive | Most diseased hearts | Staining of periostin, FAP, SMA | Periostin, mimecan, SPARC |
| Smooth muscle cells | Perivascular and reactive | Pressure overload, vasculitis | Staining of SMA | |
| Inflammatory cells | Reparative and reactive | Acute and chronic cardiac disease | Staining of macrophages, monocytes, neutrophils (CD45) | sST2, CRP, galectin‐3 |
| Content/mechanisms | ||||
| Collagen production | Structural proteins | Healthy and diseased heart | Immunostaining, rtPCR | CITP, PICP, PINP, PIIINP |
| Glycoproteins/proteoglycans | Inter‐cellular communication | Most diseased hearts | Immunostaining, rtPCR | Galectin‐3, sST2, periostin, mimecan, SPARC |
| MMP and their inhibitors (TIMPs) | Collagen degradation/production balance | Healthy and diseased heart | Immunostaining and activity assays, rtPCR | MMP‐1 and ‐9, TIMP‐1 and ‐2 |
| Growth factors: TGF, CTGF, FGF, Wnt pathways | Stimulate collagen production, affects inflammation | Most diseased heart | Immunoblots, signalling pathways | ND |
CITP, C‐terminal propeptide of procollagen type I; CRP, C‐reactive protein; MMP, matrix metalloproteinase; MRI, magnetic resonance imaging; PINP, amino‐terminal propeptide of type I collagen; PIIINP, procollagen type III N‐terminal propeptide; PINP, procollagen type I N‐terminal propeptide; rtPCR, reverse transcriptase‐polymerase chain reaction; sST2, soluble ST2; TIMP, tissue inhibitor of metalloproteinases.