Activated GDF11/8 subforms predict cardiovascular events and mortality in humans.

Ryan G Walker, Tomohiro Kato, Laura Ben Driss, Stephen A Williams, Michael A Hinterberg, Nebojsa Janjic, Amy D Gelinas, Meredith A Carpenter, Chandramohan Kattamuri, Joan E Walter, Christian Mueller, Kourtney R Mendello, Justis V Gordon, Keenan A Walker, Josef Coresh, Shalender Bhasin, Lee L Rubin, Amy J Wagers, Thomas B Thompson, Peter Ganz, Richard T Lee

Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA. · pubmed

Paper

Abstract

Circulating Growth Differentiation Factors 11 and 8 (GDF11/8) exist in both latent and active forms, and it is unclear if specific forms can predict disease outcomes. Our data suggest that a dual-specific aptamer selectively binds GDF11/8 after prodomain activation. In 11,609 patients at risk for future cardiovascular events, low dual-specific aptamer-detected GDF11/8 levels strongly predicted adverse outcomes, including cardiovascular events (HR = 0.43, p = 9.1 × 10⁻⁶³) and all-cause mortality (HR = 0.33, p = 4.8 × 10⁻⁴⁰). Use of selective aptamers suggested that results observed with the dual-specific aptamer for cardiovascular and mortality risk replicated with a GDF8 aptamer although with a smaller effect size. In a second cohort of 4110 individuals (ARIC), low dual-specific aptamer-detected GDF11/8 levels also predicted increased 8 year dementia risk (HR = 0.66, p = 0.00148). Our findings reveal that activation of GDF11/8 may be a factor in future aging-related cardiovascular and cognitive decline.

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Research summary

Low levels of activated GDF11/8 predict adverse cardiovascular events and mortality in humans. The study addresses biomarkers that may indicate underlying mechanisms of aging-related decline, linking them to cardiovascular and cognitive outcomes.

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