Abstract:Objective: To investigate the correlation between plasma levels of regulated upon activation, normal T-cell expressed and secreted (RANTES) and mammalian sterile 20-like kinase 1 (MST1) and coronary plaque burden in patients with unstable angina (UA).Methods: Hospitalized patients diagnosed with UA who underwent coronary angiography in the Department of Cardiology at the Affiliated Hospital of Chengde Medical College from January 2018 to January 2021 were selected. Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma levels of RANTES and MST1 at admission. The extent of coronary plaque burden was quantified using the SYNTAX score and Gensini score. Patients were divided into low SYNTAX score group (≤22) and medium/high SYNTAX score group (>22). Additionally, patients were divided into low RANTES group, medium RANTES group, and high RANTES group, as well as low MST1 group, medium MST1 group, and high MST1 group based on tertiles of RANTES and MST1 levels.Results: A total of 321 cases UA patients were included in the study. Plasma levels of RANTES and MST1 were significantly higher in the medium/high SYNTAX score group compared to the low SYNTAX score group (P<0.05). The SYNTAX score was higher in the high RANTES group (18.91±6.57) than in the medium RANTES group (13.69±3.05) and the low RANTES group (10.66±6.12) (P<0.05). The SYNTAX score was higher in the high MST1 group (15.75±6.13) than in the medium MST1 group (14.43±7.51) and the low MST1 group (13.06±5.28) (P<0.05). Multivariate logistic regression analysis indicated that the highest tertiles of RANTES (OR=2.67, 95%CI 1.17~6.09, P<0.05) and MST1 (OR=5.274, 95%CI 1.769~15.722, P<0.05) were independent risk factors for medium/high SYNTAX scores. The area under the receiver operating characteristic (ROC) curve (AUC) for predicting medium/high SYNTAX scores was 0.69 (95%CI0.586~0.795, P<0.05) for RANTES,0.625 (95%CI0.553~0.696, P<0.05) for MST1, and 0.786 (95%CI0.705~0.866, P<0.001) for the combination of RANTES and MST1.Conclusion: Elevated plasma levels of RANTES and MST1 are independent risk factors for higher coronary plaque burden in patients with UA.
[1] Pawluk H,Kotodziejska R,Grzesk G,et al.The potential role of RANTES in post-stroke therapy[J].Cells,2023,12(18):2217. [2] Guo Y,Kong Q,Zhang Y,et al.Elevated RANTES levels are associated with increased risk of cerebral atherosclerotic stenosis[J].BMC Neurol,2023,23(1):39. [3] Thompson B J.YAP/TAZ: drivers of tumor growth,metastasis,and resistance to therapy[J].Bioessays,2020,42(5):1900162. [4] Lee G J,Yan L,Vatner D E,et al.Mst1 inhibition rescues β1-adrenergic cardiomyopathy by reducing myocyte necrosis and non-myocyte apoptosis rather than myocyte apoptosis[J].Basic Res Cardiol,2015,110(2):7. [5] Roh K-H,Lee Y,Yoon J-H,et al.TRAF6-mediated ubiquitination of MST1/STK4 attenuates the TLR4-NF-κB signaling pathway in macrophages[J].Cell Mol Life Sci,2021,78(5):2315-2328. [6] Hu J,Wang S,Xiong Z,et al.Exosomal Mst1 transfer from cardiac microvascular endothelial cells to cardiomyocytes deteriorates diabetic cardiomyopathy[J].Biochim Biophys Acta Mol Basis Dis,2018,1864(11):3639-3649. [7] Liu Y,Zhao Y,Shukha Y,et al.Dysregulated oxalate metabolism is a driver and therapeutic target in atherosclerosis[J].Cell Rep,2021,36(4):109420. [8] Von Hundelshausen P,Weber K S,Huo Y,et al.RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium[J].Circulation,2001,103(13):1772-1777. [9] Virani S S,Nambi V,Hoogeveen R,et al.Relationship between circulating levels of RANTES (regulated on activation,normal T-cell expressed,and secreted) and carotid plaque characteristics: the atherosclerosis risk in communities (ARIC) carotid MRI study[J].Eur Heart,2011,32(4):459-468. [10] Lu K,Liu X,Guo W.Melatonin attenuates inflammation-related venous endothelial cells apoptosis through modulating the MST1-MIEF1 pathway[J].Cell Physiol,2019,234(12):23675-23684. [11] Guedeney P,Barthelemy O,Zeitouni M,et al.Prognostic value of SYNTAX score in patients with infarct-related cardiogenic shock: insights from the CULPRIT-SHOCK trial[J].JACC Cardiovasc Interv,2020,13(10):1198-1206.