Tiwari Krishna, Saravanan Aswini, Anil Abhishek, Tiwari Vikas Kumar, Shamim Muhammad Aaqib, Singh Surjit, Dwivedi Pradeep, Deora Surender, Varthya Shoban Babu
Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India.
Laboratory of Systems Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan.
Curr Cardiol Rev. 2025 Jan 7. doi: 10.2174/011573403X332671241121063641.
Cardiovascular-kidney-metabolic (CKM) syndrome is the association between obesity, diabetes, CKD (chronic kidney disease), and cardiovascular disease. GDF-15 mainly acts through the GFRAL (Glial cell line-derived neurotrophic factor Family Receptor Alpha-Like) receptor. GDF-15 and GDFRAL complex act mainly through RET co-receptors, further activating Ras and phosphatidylinositol-3-kinase (PI3K)/Akt pathways through downstream signaling. GDF-15 decreases cardiac dysfunction and hypertrophy by inducing HIF-α (hypoxia-inducible factor-1α). It causes increased fractional shortening and a significant decrease in ventricular dilation through the induction of the SMAD 2/3. GDF-15 prevents hyperglycemia-induced apoptosis in diabetes mellitus. GDF-15 causes anorexia by influencing the central systems regulating metabolism and appetite. Therefore, targeting GDF-15 can be useful for the treatment of anorexia caused by cancer as well as the prevention of resulting weight loss. GDF-15 has an important role in predicting mortality in acute kidney injury. Its high levels are related to eGFR decline and also have a prognostic role in CKD patients. Growth differentiation factor-15 (GDF-15) is a vital biomarker for diagnosis, treatment, and prognosis of CKM syndrome. Elevated GDF-15 levels can be utilised as a biomarker to determine the suitable metformin dosage. In light chain amyloidosis, a raised level of GDF-15 predicts early death in heart failure and renal disease patients. In vivo, studies using GDF-15 analogs and antibodies against GFRAL to affect metabolic parameters and ventricular dilatation have shown potential for GDF-15-based therapeutic interventions. This review aims to study the role of GDF-15 in CKM syndrome and establish it as a CKM biomarker.
心血管-肾脏-代谢（CKM）综合征是肥胖、糖尿病、慢性肾脏病（CKD）和心血管疾病之间的关联。生长分化因子15（GDF-15）主要通过胶质细胞源性神经营养因子家族受体α样受体（GFRAL）发挥作用。GDF-15与GFRAL复合物主要通过RET共受体发挥作用，通过下游信号进一步激活Ras和磷脂酰肌醇-3-激酶（PI3K）/Akt信号通路。GDF-15通过诱导缺氧诱导因子-1α（HIF-α）减轻心脏功能障碍和心肌肥厚。它通过诱导SMAD 2/3导致缩短分数增加和心室扩张显著减少。GDF-15可预防糖尿病中高血糖诱导的细胞凋亡。GDF-15通过影响调节代谢和食欲的中枢系统导致厌食。因此，靶向GDF-15可用于治疗癌症引起的厌食以及预防由此导致的体重减轻。GDF-15在预测急性肾损伤的死亡率方面具有重要作用。其高水平与估算肾小球滤过率（eGFR）下降有关，并且在CKD患者中也具有预后作用。生长分化因子15（GDF-15）是CKM综合征诊断、治疗和预后的重要生物标志物。GDF-15水平升高可作为确定合适二甲双胍剂量的生物标志物。在轻链淀粉样变性中，GDF-15水平升高预示着心力衰竭和肾病患者的早期死亡。在体内，使用GDF-15类似物和抗GFRAL抗体影响代谢参数和心室扩张的研究表明了基于GDF-15的治疗干预的潜力。本综述旨在研究GDF-15在CKM综合征中的作用，并将其确立为CKM生物标志物。
