Abstract
Transcription factor-7-like-2 (TCF7L2), a vital member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) family, plays an important role in normal human physiological and pathological processes. TCF7L2 exhibits multiple anti-atherosclerotic effects through the activation of specific molecular mechanisms, including regulation of metabolic homeostasis, macrophage polarization, and neointimal hyperplasia. A single-nucleotide substitution of TCF7L2, rs7903146, is a genetic high-risk factor for type 2 diabetes and indicates susceptibility to cardiovascular disease as a link between metabolic disorders and atherosclerosis. In this review, we summarize the anti-atherosclerosis effect and novel mechanisms underlying the function of TCF7L2 to elucidate its potential as an anti-atherosclerosis biomarker and provide a novel therapeutic target for cardiovascular diseases.
Highlights
Atherosclerosis precedes and forecasts the pathological process of cardiovascular disease (CVD), the leading cause of mortality worldwide [1, 2]
Transcription factor-7-like-2 (TCF7L2) rs7903146 induces the development of type 2 diabetes (T2D) by damaging pancreatic β-cell function and stimulating insulin resistance (IR), which causes the vascular endothelium to be more accessible to atherosclerosis [18, 63]
The activity of TCF7L2 is controlled by two contradictory regulatory elements: the co-activator β-catenin and co-repressor transducin-like enhancer of split (TLE)/Groucho [28,29,30]
Summary
Atherosclerosis precedes and forecasts the pathological process of cardiovascular disease (CVD), the leading cause of mortality worldwide [1, 2]. Wnt signaling plays a protective role in the development of atherosclerotic CVDs. Many studies have shown that Wnt signaling prevents the development of atherosclerosis via a series of processes, including glucolipid metabolism, macrophage polarization, and neointimal hyperplasia [33,34,35,36]. The Wnt signaling pathway has been proven to balance blood glucose levels and alleviate local inflammation, which is defined as an anti-atherosclerosis action.
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