Helena Grauen Larsen1, Troels Yndigegn2, Goran Marinkovic2, Helena Grufman2, Razvan Mares3, Jan Nilsson2, Isabel Goncalves1, Alexandru Schiopu4. 1. Experimental Cardiovascular Research Unit, Department of Clinical Sciences Malmö, Lund University, CRC 91:12 Jan Waldenströms gata 35, 214 28, Malmö, Sweden; Department of Cardiology, Skane University Hospital Malmö, Sweden. 2. Experimental Cardiovascular Research Unit, Department of Clinical Sciences Malmö, Lund University, CRC 91:12 Jan Waldenströms gata 35, 214 28, Malmö, Sweden. 3. University of Medicine, Pharmacy, Sciences and Technology of Tirgu-Mures, 38 Gh. Marinescu Str., Tirgu-Mures, Romania. 4. Experimental Cardiovascular Research Unit, Department of Clinical Sciences Malmö, Lund University, CRC 91:12 Jan Waldenströms gata 35, 214 28, Malmö, Sweden; Department of Cardiology, Skane University Hospital Malmö, Sweden; University of Medicine, Pharmacy, Sciences and Technology of Tirgu-Mures, 38 Gh. Marinescu Str., Tirgu-Mures, Romania. Electronic address: alexandru.schiopu@med.lu.se.
Abstract
BACKGROUND AND AIMS: The pro-inflammatory alarmin S100A12 (EN-RAGE) and the soluble form of its receptor, the receptor for advanced glycation endproducts (sRAGE), have diverging roles in cardiovascular disease. In experimental studies, S100A12 promoted atherosclerosis while sRAGE treatment was anti-atherogenic and reduced myocardial infarction size by scavenging RAGE ligands. Here, we aimed to explore the links between S100A12, sRAGE, and long-term prognosis after an acute coronary syndrome (ACS). METHODS: We measured S100A12 and sRAGE in 524 patients within 24 h after an ACS, and again 6 weeks later in a subgroup of 114 patients. This subgroup also completed a follow-up echocardiography after 1 year. The median follow-up time for recurrent major adverse cardiovascular events (MACE), defined as recurrent ACS or cardiovascular death, was 25.7 ± 12.6 months. RESULTS: In Cox proportional hazard analyses, baseline S100A12 and sRAGE were positively associated with the risk of MACE, independently of traditional cardiovascular risk factors. The association between sRAGE and MACE remained significant after additional adjustment for troponin T, NT-proBNP and hsCRP [HR 95%CI for highest versus lowest tertile 3.2 (1.5-6.5), p = 0.002]. High sRAGE was also associated with deteriorating left ventricular function and an increased rate of heart failure hospitalization post-discharge. In contrast, patients with increasing sRAGE at 6 weeks compared to baseline had lower incidence of recurrent ACS. CONCLUSIONS: Our data suggest that sRAGE has a dual, phase-dependent association with residual cardiovascular risk after ACS. These findings are important for the design and interpretation of future studies on sRAGE as biomarker and potential treatment in ACS patients.
BACKGROUND AND AIMS: The pro-inflammatory alarmin S100A12 (EN-RAGE) and the soluble form of its receptor, the receptor for advanced glycation endproducts (sRAGE), have diverging roles in cardiovascular disease. In experimental studies, S100A12 promoted atherosclerosis while sRAGE treatment was anti-atherogenic and reduced myocardial infarction size by scavenging RAGE ligands. Here, we aimed to explore the links between S100A12, sRAGE, and long-term prognosis after an acute coronary syndrome (ACS). METHODS: We measured S100A12 and sRAGE in 524 patients within 24 h after an ACS, and again 6 weeks later in a subgroup of 114 patients. This subgroup also completed a follow-up echocardiography after 1 year. The median follow-up time for recurrent major adverse cardiovascular events (MACE), defined as recurrent ACS or cardiovascular death, was 25.7 ± 12.6 months. RESULTS: In Cox proportional hazard analyses, baseline S100A12 and sRAGE were positively associated with the risk of MACE, independently of traditional cardiovascular risk factors. The association between sRAGE and MACE remained significant after additional adjustment for troponin T, NT-proBNP and hsCRP [HR 95%CI for highest versus lowest tertile 3.2 (1.5-6.5), p = 0.002]. High sRAGE was also associated with deteriorating left ventricular function and an increased rate of heart failure hospitalization post-discharge. In contrast, patients with increasing sRAGE at 6 weeks compared to baseline had lower incidence of recurrent ACS. CONCLUSIONS: Our data suggest that sRAGE has a dual, phase-dependent association with residual cardiovascular risk after ACS. These findings are important for the design and interpretation of future studies on sRAGE as biomarker and potential treatment in ACS patients.
Authors: Gary A Cuthbert; Faheem Shaik; Michael A Harrison; Sreenivasan Ponnambalam; Shervanthi Homer-Vanniasinkam Journal: Cells Date: 2020-11-10 Impact factor: 6.600
Authors: Raphael S Pinto; Guilherme S Ferreira; Gina Camillo R Silvestre; Monique de Fátima M Santana; Valéria S Nunes; Lucas Ledesma; Paula R Pinto; Sayonara Ivana S de Assis; Ubiratan F Machado; Erasmo S da Silva; Marisa Passarelli Journal: Diab Vasc Dis Res Date: 2022 Jan-Feb Impact factor: 3.541