Interplay between Senescence and Macrophages in Diabetic Cardiomyopathy: A Review of the Potential Role of GDF-15 and Klotho

• Published in: Biomedicines Vol. 12; no. 4; p. 759
• Main Authors: Almohaimeed, Ghada M, Alonazi, Asma S, Bin Dayel, Anfal F, Alshammari, Tahani K, Alghibiwi, Hanan K, Alamin, Maha A, Almotairi, Ahmad R, Alrasheed, Nouf M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2024
• Subjects: Aging; Blood levels; Blood sugar; Cardiomyopathy; Cardiovascular disease; Development and progression; Diabetes mellitus (non-insulin dependent); diabetic cardiomyopathy; GDF-15; Heart diseases; Hyperglycemia; Inflammation; Insulin resistance; Kinases; Klotho; Klotho protein; macrophage; Macrophages; Senescence; Structure-function relationships; Transforming growth factor-b; Transforming growth factors; Type 2 diabetes; Womens health; Middle East; senescence; macrophage; diabetic cardiomyopathy; Klotho; GDF-15
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines12040759

Type 2 diabetes mellitus (T2DM) is a critical health problem, with 700 million diagnoses expected worldwide by 2045. Uncontrolled high blood glucose levels can lead to serious complications, including diabetic cardiomyopathy (DCM). Diabetes induces cardiovascular aging and inflammation, increasing cardiomyopathy risk. DCM is characterized by structural and functional abnormalities in the heart. Growing evidence suggests that cellular senescence and macrophage-mediated inflammation participate in the pathogenesis and progression of DCM. Evidence indicates that growth differentiation factor-15 (GDF-15), a protein that belongs to the transforming growth factor-beta (TGF-β) superfamily, is associated with age-related diseases and exerts an anti-inflammatory role in various disease models. Although further evidence suggests that GDF-15 can preserve Klotho, a transmembrane antiaging protein, emerging research has elucidated the potential involvement of GDF-15 and Klotho in the interplay between macrophages-induced inflammation and cellular senescence in the context of DCM. This review explores the intricate relationship between senescence and macrophages in DCM while highlighting the possible contributions of GDF-15 and Klotho.