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Circulating Growth Differentiation Factors 11 and 8, Their Antagonists Follistatin and Follistatin-like-3, and Risk of Heart Failure in Elders.
Wednesday,2023-09-13 20:46 America/Los_Angeles — ecterry
| Title | Circulating Growth Differentiation Factors 11 and 8, Their Antagonists Follistatin and Follistatin-like-3, and Risk of Heart Failure in Elders. |
| Publication Type | Journal Article |
| Year of Publication | 2023 |
| Authors | Kizer, JR, Patel, S, Ganz, P, Newman, AB, Bhasin, S, Lee, S-J, Cawthon, PM, LeBrasseur, N, Shah, SJ, Psaty, BM, Tracy, RP, Cummings, SR |
| Journal | J Gerontol A Biol Sci Med Sci |
| Date Published | 2023 Aug 25 |
| ISSN | 1758-535X |
| Abstract | <p><b>BACKGROUND: </b>Heterochronic parabiosis has identified growth differentiation factor (GDF)-11 as a potential means of cardiac rejuvenation, but findings have been inconsistent. A major barrier has been lack of assay specificity for GDF-11 and its homolog GDF-8.</p><p><b>METHODS: </b>We tested the hypothesis that GDF-11 and GDF-8, and their major antagonists follistatin and follistatin-like (FSTL)-3, are associated with incident heart failure (HF) and its subtypes in elders. Based on validation experiments, we used liquid chromatography tandem mass spectrometry to measure total serum GDF-11 and GDF-8, along with follistatin and follistatin-like (FSTL)-3 by immunoassay, in two longitudinal cohorts of older adults.</p><p><b>RESULTS: </b>In 2,599 participants (age 75.2±4.3) followed for 10.8±5.6 years, 721 HF events occurred. After adjustment, neither GDF-11 (HR per doubling: 0.93 [0.67, 1.30]) nor GDF-8 (HR: 1.02 per doubling [0.83, 1.27]) was associated with incident HF or its subtypes. Positive associations with HF were detected for follistatin (HR: 1.15 [1.00, 1.32]) and FLST-3 (HR: 1.38 [1.03, 1.85]), and with HF with preserved ejection fraction for FSTL-3 (HR: 1.77 [1.03, 3.02]). (All HRs per doubling of biomarker.) FSTL-3 associations with HF appeared stronger at higher follistatin levels and vice versa, and also for men, Blacks and lower kidney function.</p><p><b>CONCLUSIONS: </b>Among older adults, serum follistatin and FSTL-3, but not GDF-11 or GDF-8, were associated with incident HF. These findings do not support the concept that low serum levels of total GDF-11 or GDF-8 contribute to HF late in life, but do implicate transforming growth factor-βsuperfamily pathways as potential therapeutic targets.</p> |
| DOI | 10.1093/gerona/glad206 |
| Alternate Journal | J Gerontol A Biol Sci Med Sci |
| PubMed ID | 37624693 |
| Grant List | R01 AG052964 / AG / NIA NIH HHS / United States |
ePub date:
23/08