Review of Galectin-3 and the Collagen Marker PIIINP in Myocardial Fibrosis in Dilated Cardiomyopathy: Predictive Value for Major Adverse Cardiovascular Events

Dilated cardiomyopathy (DCM) is characterized by ventricular dilation and systolic dysfunction, and the associated pathophysiology is closely linked to myocardial fibrosis, a key contributor to disease progression and poor prognosis. Galectin-3 (Gal-3) plays a crucial role in initiating early proinflammatory and profibrotic signaling. Meanwhile, type III procollagen N-terminal propeptide (PIIINP) serves as a marker of type III collagen synthesis and acts as an active profibrotic effector. The counterpart to PIIINP, type III procollagen C-terminal propeptide (PIIICP), is released during type III collagen maturation, reflecting distinct processing and clearance dynamics. PIIINP promotes fibrosis through integrin α2β1/discoidin domain receptor 1 (DDR1)-mediated extracellular signal-regulated kinase (ERK)/phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling and contributes to the establishment of a Gal-3–transforming growth factor-β (TGF-β)–PIIINP positive feedback loop, thereby linking inflammation to extracellular matrix deposition. Recently, Gal-3 and PIIINP have gained recognition as valuable biomarkers for the diagnosis, risk stratification, and prognosis assessment of DCM. Unlike previous reviews that focused solely on individual fibrosis markers or static histological assessments, this review uniquely highlights the complementary roles of Gal-3 and PIIINP. These markers are crucial for understanding inflammatory-fibrotic activation and dynamic collagen turnover. This review systematically outlines the expression patterns of these markers across various stages of DCM and underscores the additional prognostic value of the associated combined detection beyond traditional indicators. Among the components of major adverse cardiovascular events (MACE), heart failure hospitalization and cardiovascular mortality are most strongly associated with elevated levels of Gal-3 and PIIINP in patients with DCM. Specifically, Gal-3 levels of ≥14.54 ng/mL are closely linked to increased risks of heart failure readmission and sudden cardiac death. In contrast, elevated PIIINP levels are most strongly associated with heart failure hospitalization and ventricular arrhythmias. This review aims to elucidate the specific biological functions of Gal-3 and PIIINP, address both mechanistic and clinical uncertainties, and summarize evidence-based thresholds for risk stratification. This review also seeks to provide theoretical insights and clinical guidance for early intervention and personalized anti-fibrotic therapy in DCM. A systematic search was conducted in PubMed, Embase, and Web of Science, covering literature from inception to March 2026. The search used keywords such as “dilated cardiomyopathy”, “myocardial fibrosis”, “Galectin-3”, “PIIINP”, “biomarker”, and “cardiovascular events”. The review included studies comprising clinical trials, observational research, and mechanistic investigations of Gal-3 and PIIINP in DCM. Reviews, case reports, and non-English literature were excluded. Data were synthesized using a narrative review approach.