These genes synergistically drive HF progression through a three-pronged mechanism: C5AR1/HCLS1-mediated immune cell infiltration amplifies inflammation (35, 36); TIMP1-mediated MMP inhibition accelerates fibrotic remodeling; LAPTM5-promoted TNF-α/IL-1β secretion suppresses mitochondrial function, forcing a reliance on glycolytic energy production. Here, HCLS1 is linked to hydrops fetalis.