Interleukin-6 and adhesion molecules VCAM-1 and ICAM-1 as biomarkers of post-acute myocardial infarction heart failure

Abstract

Acute coronary syndromes are associated with a high prevalence of complications including heart failure (HF). The aim of this study was to investigate the association of novel biomarkers with the occurrence of post-acute myocardial infarction (AMI) HF. A prospective study was conducted with patients admitted to the emergency department with ST-segment elevation myocardial infarction (STEMI). Blood and urine samples were collected for analysis of traditional and novel biomarkers, including interleukin-6, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). We compared the levels of these biomarkers between patients with and without post-STEMI HF. A total of 48 patients were assessed, with a prevalence of males. Fifteen patients (31.2%) had post-STEMI HF. Patients with HF had higher mean values of IL-6, VCAM-1, and ICAM-1 compared to those who did not develop HF (57.06 vs 14.03 pg/mL, P=0.001; 1719.58 vs 1304.34 ng/mL, P=0.001; and 1594.20 vs 1158.74 ng/mL, P<0.001, respectively). The three biomarkers were shown to be good predictors of post-STEMI HF (IL-6: AUC 0.786, P=0.002; VCAM-1: AUC 0.797, P=0.001; and ICAM-1: AUC 0.825, P<0.0001), with the respective cutoff points being calculated based on the best sensitivity and specificity indexes (IL-6: 8.67 pg/mL; VCAM-1: 1501.42 ng/mL; and ICAM-1: 1262.38 ng/mL). Of the three biomarkers, only VCAM-1 and ICAM-1 had a direct linear association between them (r=0.470, P<0.0001). IL-6, VCAM-1, and ICAM-1 were associated with the development of new post-AMI HF symptoms, but only VCAM-1 and ICAM-1 correlated with each other, possibly because they have the same pathophysiological mechanism of action.

Oxidative Stress and Inflammation Biomarker Expression in Obstructive Sleep Apnea Patients

“…However, despite obesity and hypertension are comorbidities associated with augmented chemoreflex patients, the CPAP treatment has not demonstrated significant results on the sympathetic system activity [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ,…”

“…Reactive oxygen species (ROS) in particular, cause damage to the vascular endothelium from the early stages of the disease and stimulates the expression of the adhesion molecules of leukocytes (L-selectin, integrins) and related endothelial adhesion molecules (E-selectin, P-selectin, ICAM-1, VECAM-1) [ 19 , 20 ]. Endothelial lesion resulting from these biomolecular alterations, it would seem to lead to the microvascular damage of patients with OSAS [ 19 ].…”

Inflammatory Markers Related to Innate and Adaptive Immunity in Atherosclerosis: Implications for Disease Prediction and Prospective Therapeutics

“… 132 It was also observed that ICAM-1 and VCAM-1 were associated with the development of new post-acute myocardial infarction symptoms in patients with heart failure. 133 Several inflammatory mediators, such as tumor necrosis factor (TNF)-α, are able to enhance the surface expression of adhesion molecules on the vessel endothelial cells. 134 Another study suggested the potential of soluble biomarkers in monitoring endothelial dysfunction, including E selectin, von Willebrand factor, soluble endothelial cell protein C receptor, thrombomodulin, and tissue plasminogen activator.…”

“…NGAL confers a high predictive score for future cardiovascular events in individuals without established cardiovascular disease [ 130 , 174 ] Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion protein-1 (VCAM-1) Innate/adaptive immunity and endothelial dysfunction Upregulation of ICAM-1 and VCAM-1 on endothelial cells contributes to infiltration of inflammatory cells to vessel wall Increased serum levels of ICAM-1 and VCAM-1 in patients with heart failure. ICAM-1 and VCAM-1 are associated with the development of new post-acute myocardial infarction symptoms in heart failure subjects [ 133 ] Endothelial microparticle (EMPs)/endothelial progenitor cells (EPCs) Endothelial dysfunction EMPs are secreted during endothelial injury Levels of endothelial injury-related factor EMPs are increased in the serum of individuals at risk for cardiovascular diseases, while the quantity of endothelial repair-associating factor EPCs is reduced [ 137–139 ] Reactive oxygen species (ROS) Endothelial dysfunction High levels of ROS promote endothelial dysfunction High levels of ROS lead to upregulation of adhesion molecules, apoptosis of vessel endothelial cells, activation of MMPs, lipid oxidation, and endothelial dysfunction [ 151–154 ] Chromosome 9p21 (Chr9p21) genotype Genetics Expression of transcripts adjacent to the Chr9p21 locus of coronary artery disease is affected by the genotype at this locus and associated with atherosclerosis risk Antisense non-coding RNA in the INK4 locus (ANRIL, which is adjacent to the Chr9p21 locus) is associated with atherosclerosis and Chr9p21 genotype [ 168–170 ] Phosphodiesterase 4D ( PDE4D ) gene rs966221 polymorphism Genetics In vascular smooth muscle and endothelial cells, PDE4D participates in intracellular signaling pathways that modulate the concentration of cyclic adenosine monophosphate (cAMP), a secondary messenger critical to vascular function rs966221 polymorphism may be a valuable biomarker for predicting the risk of recurrence in ischemic stroke patients with large artery atherosclerosis [ 172 ] …”

Brain-derived neurotrophic factor gene polymorphism in post-ST-elevation myocardial infarction patients undergoing primary percutaneous intervention

“…that are designed for risk stratification among patients with STEMI [4][5][6] , the risk assessment and prediction of poor clinical outcomes after successful competed PPCI in post-STEMI patients are uncertain 7 . There are several limitations that could decrease the predictive value of conventional biomarkers in post-STEMI individuals, such as older age, morbid obesity, diabetes mellitus (DM), preserved or normal left ventricular (LV) ejection fraction (EF), co-existing kidney insufficiency and atrial fibrillation [8][9][10] . Neurotrophins are a superfamily of regulatory proteins which regulate proliferation, differentiation, survival and plasticity of neurons 11 .…”