Scientists have uncovered the protecting position of the protein GADD45A in guarding the guts from dangerous stress responses.
When the guts is positioned below larger pressure, its ventricular wall can thicken, a course of often known as cardiac hypertrophy. This modification is a pure adjustment that helps ease stress on the guts and keep its perform. In lots of circumstances it may be reversed with out lasting penalties, but when the pressure continues over time, the situation could progress to pathological hypertrophy, which might trigger extra extreme issues (dilatation of the ventricular cavities, adjustments in cardiac efficiency, coronary heart failure, and many others.).
People with diabetes, significantly these with sort 2 diabetes (DM2), face a better threat of coronary heart failure due to widespread contributing elements (hypertension, weight problems, coronary coronary heart illness, and many others.).
A current examine revealed in Mobile and Molecular Life Sciences has revealed a brand new issue concerned within the improvement of pathological hypertrophy. The findings point out that boosting the exercise of the GADD45A protein could supply a possible therapeutic strategy to sluggish the advance of this damaging coronary heart situation.
The examine is led by Professor Manuel Vázquez-Carrera and Affiliate Professor Xavier Palomer, from the UB’s School of Pharmacy and Meals Sciences, the Institute of Biomedicine of the UB (IBUB) and the Sant Joan de Déu Analysis Institute (IRSJD), and the CIBER’s space of Diabetes and Related Metabolic Ailments (CIBERDEM). The primary writer of the article is the knowledgeable Adel Rostami (UB-IBUB-IRSJD-CIBERDEM).
An element with a outstanding position in cardiac perform
The GADD45A (progress arrest and DNA damage inducible 45A) protein is a multifunctional factor associated with stress signalling and cell damage. In this study, the team assessed the role of GADD45A in cardiac function using animal models and human cardiac cells.
The main mechanisms involved in pathological hypertrophy include inflammatory processes, fibrosis, mitochondrial dysfunction, dysregulation of calcium-handling proteins, metabolic alterations, cardiomyocyte hypertrophy, and cell death. Fibrosis and inflammation are key factors in the progression of this pathological cardiac hypertrophy and subsequent heart failure.
“Fibrosis, in particular, correlates directly with the development of the disease and with adverse clinical outcomes, and has a major impact on the clinical condition of the patient,” says Professor Manuel Vázquez-Carrera.
The results reveal that the lack of GADD45A factor in mice triggers cardiac fibrosis, inflammation, and apoptosis. These changes correlate with hyperactivation of the proinflammatory and profibrotic transcription factors AP-1 (activator protein-1), NF-κB (nuclear factor-κB), and STAT3 (signal transducer and activator of transcription 3).
According to the findings, deletion of GADD45A also caused substantial cardiac hypertrophy that negatively affected cardiac morphology and function in mice lacking this protein. Furthermore, overexpression of GADD45A in human AC16 cardiomyocytes partially prevented the inflammatory and fibrotic response induced by tumor necrosis factor-alpha (TNF-α).
“Taken together, the data presented in this study highlight an important role for GADD45A protein in the heart, as it may prevent inflammation, fibrosis and apoptosis and thus preserve cardiac function,” says Xavier Palomer.
This paper expands our knowledge of the action mechanisms of GADD45A in the body. To date, previous studies have identified the role as a tumor suppressor in cancer development, as well as its involvement in the regulation of catabolic and anabolic metabolic pathways and in the prevention of inflammation, fibrosis, and oxidative stress in some tissues and organs. Finally, some studies have indicated that the modulation of GADD45A could be a suitable therapeutic strategy to prevent obesity and diabetes.
Reference: “GADD45A suppression contributes to cardiac remodeling by promoting inflammation, fibrosis and hypertrophy” by Adel Rostami, Xavier Palomer, Javier Pizarro-Delgado, Lucía Peña, Mònica Zamora, Marta Montori-Grau, Emma Barroso, Brenda Valenzuela-Alcaraz, Fàtima Crispi, Jesús M. Salvador, Raquel García, María A. Hurlé, Francisco Nistal and Manuel Vázquez-Carrera, 30 April 2025, Cellular and Molecular Life Sciences.
DOI: 10.1007/s00018-025-05704-x
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