GDF-11

Summary

GDF-11 is a TGF-beta superfamily signaling protein studied mainly as an endogenous regulator and circulating biomarker rather than as an established administered drug. Reviews note ongoing controversy over its biological role and whether it can serve as a therapeutic agent, while circulating GDF-11 levels have been correlated with outcomes in cardiovascular disease, cancer, and uremia, supporting its candidacy as a disease biomarker ^[2]. It has been proposed as a potential cardiac pro-angiogenic factor, and companies are pursuing GDF-11 to restore regenerative capacity, but this remains developmental ^[1]. Mechanistic human-tissue work shows GDF-11 acts via ALK4/ALK5 receptors and SMAD2/3 signaling to regulate placental hCG expression and trophoblast invasion, with serum GDF-11 markedly reduced in preeclampsia ^[3,4]. The provided literature contains no interventional randomized trials of administering GDF-11 therapeutically, so its clinical evidence as a treatment is preliminary and largely target/biomarker-based.

Sources

1. 1. GDF-11 as a Potential Cardiac Pro-Angiogenic Factor JACC. Basic to translational science, 2023.
2. 2. The versatility and paradox of GDF 11 Pharmacology & therapeutics, 2017.
3. 3. GDF-11 downregulates placental human chorionic gonadotropin expression by activating SMAD2/3 signaling Cell communication and signaling : CCS, 2023.
4. 4. GDF-11 stimulates human extravillous trophoblast cell invasion by upregulating ANGPTL4 expression Reproduction (Cambridge, England), 2025.

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