Central Diagnostics Laboratory, Division Laboratory, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
Curr Atheroscler Rep. 2024 May;26(5):163-175. doi: 10.1007/s11883-024-01196-5. Epub 2024 May 3.
Fatty acid-binding protein 4 (FABP4) plays a role in lipid metabolism and cardiovascular health. In this paper, we cover FABP4 biology, its implications in atherosclerosis from observational studies, genetic factors affecting FABP4 serum levels, and ongoing drug development to target FABP4 and offer insights into future FABP4 research.
FABP4 impacts cells through JAK2/STAT2 and c-kit pathways, increasing inflammatory and adhesion-related proteins. In addition, FABP4 induces angiogenesis and vascular smooth muscle cell proliferation and migration. FABP4 is established as a reliable predictive biomarker for cardiovascular disease in specific at-risk groups. Genetic studies robustly link PPARG and FABP4 variants to FABP4 serum levels. Considering the potential effects on atherosclerotic lesion development, drug discovery programs have been initiated in search for potent inhibitors of FABP4. Elevated FABP4 levels indicate an increased cardiovascular risk and is causally related to acceleration of atherosclerotic disease, However, clinical trials for FABP4 inhibition are lacking, possibly due to concerns about available compounds' side effects. Further research on FABP4 genetics and its putative causal role in cardiovascular disease is needed, particularly in aging subgroups.
脂肪酸结合蛋白 4(FABP4)在脂质代谢和心血管健康中发挥作用。本文综述了 FABP4 的生物学特性、观察性研究中其在动脉粥样硬化中的作用、影响 FABP4 血清水平的遗传因素,以及目前针对 FABP4 的药物研发情况,并对未来的 FABP4 研究提供了一些见解。
FABP4 通过 JAK2/STAT2 和 c-kit 途径影响细胞,增加炎症和黏附相关蛋白。此外,FABP4 还诱导血管生成以及血管平滑肌细胞的增殖和迁移。在特定的高危人群中,FABP4 已被确立为心血管疾病可靠的预测生物标志物。遗传研究强有力地将 PPARG 和 FABP4 变体与 FABP4 血清水平联系起来。鉴于其对动脉粥样硬化病变发展的潜在影响,已启动了药物发现计划,以寻找 FABP4 的有效抑制剂。升高的 FABP4 水平表明心血管风险增加,并且与动脉粥样硬化疾病的加速发展有关。然而,目前缺乏针对 FABP4 抑制的临床试验,这可能是由于对现有化合物副作用的担忧。需要进一步研究 FABP4 的遗传学及其在心血管疾病中的潜在因果作用,特别是在老龄化亚组中。