Interleukin-1α Is a Central Regulator of Leukocyte-Endothelial Adhesion in Myocardial Infarction and in Chronic Kidney Disease

Abstract

Background: Cardiovascular diseases (CVD) and chronic kidney disease (CKD) are highly prevalent, aggravate each other, and account for substantial mortality. Both conditions are characterized by activation of the innate immune system. The alarmin IL-1α is expressed in a variety of cell types promoting (sterile) systemic inflammation. The aim of the present study was to examine the role of IL-1α in mediating inflammation in the setting of acute myocardial infarction (AMI) and CKD. Methods: We assessed the expression of IL-1α on the surface of monocytes from patients with AMI and patients with CKD and determined its association with atherosclerotic CVD events during follow-up in an explorative clinical study. Furthermore, we assessed the inflammatory effects of IL-1α in several organ injury models in Il1a -/- and Il1b -/- mice and investigated the underlying mechanisms in vitro in monocytes and endothelial cells. Results: IL-1α is strongly expressed on the surface of monocytes from patients with AMI and CKD compared to healthy controls. Higher IL-1α surface expression on monocytes from patients with AMI and CKD was associated with a higher risk for atherosclerotic CVD events, which underlines the clinical relevance of IL-1α. In mice, IL-1α, but not IL-1β, mediates leukocyte-endothelial adhesion as determined by intravital microscopy. IL-1α promotes accumulation of macrophages and neutrophils in inflamed tissue in vivo . Furthermore, IL-1α on monocytes stimulates their homing at sites of vascular injury. A variety of stimuli such as free fatty acids or oxalate crystals induce IL-1α surface expression and release by monocytes, which then mediates their adhesion to the endothelium via IL-1 receptor-1. Besides, IL-1α promotes expression of the vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells thereby fostering the adhesion of circulating leukocytes. IL-1α induces inflammatory injury after experimental AMI and abrogation of IL-1α prevents the development of CKD in oxalate or adenine-fed mice. Conclusions: IL-1α represents a key mediator of leukocyte-endothelial adhesion and inflammation in AMI and CKD. Inhibition of IL-1α may serve as a novel anti-inflammatory treatment strategy.

Serum VCAM‐1 and ICAM‐1 measurement assists for MACE risk estimation in ST‐segment elevation myocardial infarction patients

“…The current study discovered that both VCAM‐1 and ICAM‐1 were positively linked with MACE risk. The potential explanation would be that: (1) elevated VCAM‐1 facilitated the adhesion of circulating leukocytes 23 ; meanwhile, VCAM‐1 might promote adhesion and infiltration of monocytes into the endothelium 24 ; these processes boosted the progression of cardiac diseases; therefore, VCAM‐1 could forecast elevated MACE risk in STEMI patients; (2) raised ICAM‐1 might foster fibrosis, vascular hypertrophy, macrophage infiltration, as well as reactive oxygen species production, resulting in the incidence of MACE 25 ; therefore, elevated ICAM‐1 also had the potency to predict higher MACE risk in STEMI patients.…”

“…Possible arguments would be that: (1) regarding age, STEMI patients with age ≥65 years were more likely to suffer from myocardial infarction, heart failure, cardiac death, etc 26–28 29 ; (3) inflammation participated in the progression of cardiovascular diseases, and CRP could reflect inflammation status 23,30,31 ; (4) STEMI patients with the multivessel disease were susceptible to MACE 32 ; therefore, abovementioned factors independently predicted MACE risk in STEMI patients. A subsequent prediction model performed by nomogram provided a reference for predicting the MACE risk at 1, 2, and 3 years; meanwhile, the ROC curve analysis suggested that this multivariate prediction model performed by nomogram may assist in MACE prediction for STEMI patients.…”

Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review

“…Endothelial cells produce NO via endothelial nitric oxide synthase (eNOS) in the vessel wall [ 63 ], which hence regulates blood pressure and blood flow and it also inhibits oxidation of LDL [ 18 , 64 ]. Endothelial cells adhere to circulating leukocytes via vascular cell adhesion molecule-1 (VCAM-1) on their cell surface [ 65 ]. Endothelial cells assimilate oxidized LDL via low-density lipoprotein receptor-1 (LOX-1), which is conducive to the development of atherosclerotic plaques [ 66 ].…”

Biomarkers and Predictors of Adverse Cardiovascular Events in Different Stages of Chronic Kidney Disease

“…Recently published research by Schunk et al demonstrated that IL-1α represents a central regulator of leukocyte-endothelial adhesion in myocardial infarction and in chronic kidney disease, so inhibition of IL-1α may serve as a novel anti-inflammatory treatment strategy for this population. 46…”