The Role of Growth Differentiation Factor 15 in Energy Metabolism

Aims: Despite several clinical risk factors for atrial fibrillation (AF), some newly identified biomarkers may also potentially serve as risk factors for AF. However, none of these factors so far have been adopted in clinical practice. Recently, a number of studies with an attempt to identify the role of growth differentiation factor 15 (GDF-15) in AF have obtained ambiguous results. We try to identify the predicting role of GDF-15 in AF and AF-related complications with meta-analysis or systematic analysis. Methods and results: We enrolled 10 studies, looking at the predicting role of GDF-15 in non-valvular AF using meta-analysis, summarized its role in AF-related major complications, and discussed whether it was dependable to forecast postoperative AF. It turned out that GDF-15 is an independent factor to predict occurrence of AF, while it remains obscure to directly demonstrate its relationship with postoperative AF. For AF patients on anti-platelet treatment, GDF-15 plays a critical role in predicting major bleeding, cardiovascular death and overall death, and improves the current predicting model. Conclusions: Circulating GDF-15 greatly associates with AF and AF-related complications. It should be applied clinically.

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Role of Growth Differentiation Factor 15 in Lung Disease and Senescence: Potential Role Across the Lifespan

Frontiers in Medicine ◽

10.3389/fmed.2020.594137 ◽

2020 ◽

Vol 7 ◽

Author(s):

Faeq Al-Mudares ◽

Samuel Reddick ◽

Jenny Ren ◽

Akshaya Venkatesh ◽

Candi Zhao ◽

...

Keyword(s):

Cellular Senescence ◽

Transforming Growth Factor Beta ◽

Lung Diseases ◽

Transforming Growth Factor ◽

Pathological Condition ◽

Premature Neonate ◽

Chronic Obstructive ◽

Growth Differentiation Factor 15 ◽

Differentiation Factor

Growth Differentiation Factor 15 (GDF15) is a divergent member of transforming growth factor-beta (TGF-β) superfamily and is ubiquitously expressed, under normal physiological conditions. GDF15 expression increases during many pathological states and serves a marker of cellular stress. GDF15 has multiple and even paradoxical roles within a pathological condition, as its effects can be dose- and time-dependent and vary based on the targeted tissues and downstream pathways. GDF15 has emerged as one of the most recognized proteins as part of the senescence associated secretory phenotype. Cellular senescence plays a major role in many lung diseases across the life-span from bronchopulmonary dysplasia in the premature neonate to COPD and idiopathic pulmonary fibrosis in aged adults. GDF15 levels have been reported to be as a useful biomarker in chronic obstructive pulmonary disease, lung fibrosis and pulmonary arterial hypertension and predict disease severity, decline in lung function and mortality. Glial-cell-line-derived neurotrophic factor family receptor alpha-like (GFRAL) in the brain stem has been identified as the only validated GDF15 receptor and mediates GDF15-mediated anorexia and wasting. The mechanisms and pathways by which GDF15 exerts its pulmonary effects are being elucidated. GDF15 may also have an impact on the lung based on the changes in circulating levels or through the central action of GDF15 activating peripheral metabolic changes. This review focuses on the role of GDF15 in different lung diseases across the lifespan and its role in cellular senescence.

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