Impact of follistatin-like 1 on cardiac repair processes following myocardial infarction

FIGURE 1. Schematic representation of the FSTL1 protein and its structural domains. Key domains include the signal peptide (SP), N-terminal domain (ND), follistatin-like domain (FOLN), Kazal-like domain (Kazal), EF-hand domains (EF1/2), von Willebrand factor type C domain (vWFC), and the C-terminal domain (CD) enriched with acidic L-amino acids.

FIGURE 2. Time-linked switch model for the dual role of FSTL1 after myocardial infarction. Early FSTL1 (cardiomyocyte/endothelial-dominant) promotes cardioprotection and angiogenic repair (e.g., AMPK/PI3K–Akt; DIP2A-associated signaling), whereas late FSTL1 (fibroblast-dominant) biases toward profibrotic remodeling (e.g., TGF-β-related pathways and MAPK cascades). Microenvironmental cues and FSTL1 glycosylation state modulate receptor/pathway selection across phases.

FIGURE 3. Pro-angiogenic mechanisms of FSTL1 in post-MI cardiac repair. FSTL1 derived from the heart and skeletal muscle enters the circulation and binds to its receptor DIP2A on endothelial cells. Downstream, the DIP2A–PI3K/Akt/eNOS–NO axis and the AMPK–HIF-1α/PGC-1α module have been implicated in promoting endothelial cell proliferation, migration, survival, and angiogenic factor expression (VEGF, FGF2, Angpt-1), ultimately enhancing neovascularization. Additional proposed branches (e.g., VEGFR2-associated signaling, Ras/MEK/ERK, and TGF-β/Smad2/3) are indicated as reported mechanisms. Black arrows represent activation or upregulation.