Growth stimulation expressed gene 2 (ST2): Clinical research and application in the cardiovascular related diseases

Abstract

As an interleukin (IL)-1 receptor family member, scientists found that when circulating soluble growth stimulation expressed gene 2 (sST2) is low, its ligand, IL-33, will bind to ST2L to exert protective effects on various types of cells. On the other hand, competitive binding of IL-33 occurs when sST2 concentrations are increased, followed by a reduction in the amount available for cell protection. Based on this mechanism, the usage of sST2 is to identify the population of high-risk patients with cardiovascular disease. In recent years, the role of serum sST2 in the occurrence, diagnosis, prognosis, and treatment of cardiovascular diseases has been gradually accepted by doctors. This manuscript systemically reviews the biological functions and applications of sST2 in disease diagnosis and treatment, especially for cardiovascular diseases. In clinical testing, since IL-33 can negatively impact sST2 measurement accuracy, the properties of current assay kits have been summarized and discussed to provide a clear view of the clinical chemistry results. Although sST2 is a promising biomarker, there are few quantitative approaches available for clinical testing. In this context, a mass spectrometry (MS)-based approach might be an option, as this is a powerful analytical tool to distinguish structurally related molecules in the matrix and decrease false-positive results in clinical testing. Moreover, approaches developed based on MS would be an ideal way to further study sST2 standardization.

Novel Biomarkers in Early Detection of Heart Failure: A Narrative Review

“…IL-33 is an IL-1-like cytokine released by stromal cells in cardiac and extracardiac tissues in response to cell injury [ 130 ]. By attaching to the transmembrane receptor ST2L isoform, IL-33 produces beneficial effects such as lowering myocardial fibrosis and cardiomyocyte hypertrophy in response to angiotensin 11 or phenylephrine and apoptosis by inducing antiapoptotic factors and suppression of caspase three activities [ 131 ].…”

“…Research has also demonstrated that as sST2 is less affected by renal function than BNP, it can be utilized in conjunction with BNP as an additional diagnostic marker for HF [ 134 ]. NTPro-BNP and sST2 both exhibited a high diagnostic accuracy for HF in a single-center study, but sST2 had an even better prediction capacity for fatal outcomes, including in-hospital and one-month mortality rates [ 130 ]. The function of sST2 in characterizing AHF in individuals presenting with acute dyspnea was examined in the PRIDE trial.…”

Effect of combining sST2/HDL-C ratio with risk factors of coronary heart disease on the detection of angina pectoris in Chinese: a retrospective observational study

“…One is membrane-bound form ST2 (ST2L), which can bind to IL-33, playing a role in preventing hypertrophy and fibrosis and modulation of Th1/Th2; while the other is sST2, which acts as a decoy receptor, binding to free IL-33 and blocking ST2/IL-33 signaling (10,11). Many studies have shown that soluble ST2 is associated with the development of cardiovascular disease (CVD) such as aortic dissection, heart failure, acute coronary syndrome and atrial fibrillation (12)(13)(14)(15). The presence of inflammatory cells in coronary plaques from patients with UAP provides the basis for the atherosclerotic inflammatory hypothesis that was supported by plenty of evidence (16,17).…”