Inflammatory Mechanisms Contributing to Endothelial Dysfunction

Published on Jul 6, 2021in Biomedicines6.081
· DOI :10.3390/BIOMEDICINES9070781
Panagiotis Theofilis5
Estimated H-index: 5
Marios Sagris5
Estimated H-index: 5
+ 4 AuthorsDimitris Tousoulis47
Estimated H-index: 47
Maintenance of endothelial cell integrity is an important component of human health and disease since the endothelium can perform various functions including regulation of vascular tone, control of hemostasis and thrombosis, cellular adhesion, smooth muscle cell proliferation, and vascular inflammation. Endothelial dysfunction is encompassed by complex pathophysiology that is based on endothelial nitric oxide synthase uncoupling and endothelial activation following stimulation from various inflammatory mediators (molecular patterns, oxidized lipoproteins, cytokines). The downstream signaling via nuclear factor-κB leads to overexpression of adhesion molecules, selectins, and chemokines that facilitate leukocyte adhesion, rolling, and transmigration to the subendothelial space. Moreover, oscillatory shear stress leads to pro-inflammatory endothelial activation with increased monocyte adhesion and endothelial cell apoptosis, an effect that is dependent on multiple pathways and flow-sensitive microRNA regulation. Moreover, the role of neutrophil extracellular traps and NLRP3 inflammasome as inflammatory mechanisms contributing to endothelial dysfunction has recently been unveiled and is under further investigation. Consequently, and following their activation, injured endothelial cells release inflammatory mediators and enter a pro-thrombotic state through activation of coagulation pathways, downregulation of thrombomodulin, and an increase in platelet adhesion and aggregation owing to the action of von-Willebrand factor, ultimately promoting atherosclerosis progression.
#1Aldo Bonaventura (UniGe: University of Genoa)H-Index: 28
#2Alessandra Vecchié (VCU: Virginia Commonwealth University)H-Index: 16
Last. Antonio Abbate (VCU: Virginia Commonwealth University)H-Index: 79
view all 11 authors...
Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in s...
#1Baochen Bai (Qingdao University)H-Index: 4
#3Shengxiang Ji (CDC: Centers for Disease Control and Prevention)H-Index: 2
Last. Xian-ming Chu (Qingdao University)H-Index: 5
view all 9 authors...
Inflammation and endothelial dysfunction are important participants and drivers in atherosclerosis. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation and the resulting pyroptosis are involved in the initiation and vicious circle of chronic inflammation, thus playing an indispensable role in atherosclerosis. Accordingly, blocking the activation of NLRP3 inflammasome may be a promising treatment strategy to blunt the progression of atherosclerosis. In this study, it ...
#1Brittany Weber (Brigham and Women's Hospital)H-Index: 7
#2Emma Stevens (Brigham and Women's Hospital)H-Index: 4
Last. Marcelo F. Di Carli (Brigham and Women's Hospital)H-Index: 84
view all 16 authors...
OBJECTIVES The purpose of this study was to evaluate the prognostic value of quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR), reflecting the integrated effects of diffuse atherosclerosis and microvascular dysfunction in patients with systemic inflammatory disorders. BACKGROUND Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis (PsO) are common inflammatory conditions with excess cardiovascular (CV) risk compared to the general population. Syst...
#3Hui Chen (HKU: University of Hong Kong)H-Index: 245
Nuclear factor kappa B (NF-κB) activation contributes to many vascular inflammatory diseases. The present study tested the hypothesis that microRNA-17-3p (miR-17-3p) suppresses the pro-inflammatory responses via NF-κB signaling in vascular endothelium. Human umbilical vein endothelial cells (HUVECs), transfected with or without miR-17-3p agomir/antagomir, were exposed to lipopolysaccharide (LPS), and the inflammatory responses were determined. The cellular target of miR-17-3p was examined with d...
#1Konstantinos Mourouzis (UoA: National and Kapodistrian University of Athens)H-Index: 11
#2Gerasimos Siasos (UoA: National and Kapodistrian University of Athens)H-Index: 50
Last. Dimitris Tousoulis (UoA: National and Kapodistrian University of Athens)H-Index: 47
view all 11 authors...
BACKGROUND Lipoprotein-associated Phospholipase A2 (Lp-PLA2), can exert proinflammatory as well as proatherogenic properties on the vascular wall. The current study sought to evaluate the influence of high Lp-PLA2 levels on indices of arterial wall properties in patients with stable coronary artery disease (CAD). METHODS Three hundred seventy-four consecutive patients with stable CAD (mean age 61 ± 11 years, 89% males) were enrolled in this single-center cross-sectional study. Flow-mediated dila...
#1Tapan Behl (Chitkara University)H-Index: 17
#2Eshita Sharma (Chitkara University)H-Index: 3
Last. Simona Bungau (University of Oradea)H-Index: 20
view all 10 authors...
Diabetes mellitus (DM) has become one of the major healthcare challenges worldwide in the recent times and inflammation being one of its key pathogenic process/mechanism affect several body parts including the peripheral and central nervous system. High-mobility group box 1 (HMGB1) is one of the major non-histone proteins that plays a key role in triggering the inflammatory response. Upon its release into the extracellular milieu, HMGB1 acts as an "alarmin" for the immune system to initiate tiss...
#1Carmen De Miguel (UAB: University of Alabama at Birmingham)H-Index: 12
#2Pablo PelegrínH-Index: 56
Last. Santiago CuevasH-Index: 10
view all 4 authors...
Inflammasomes are components of the innate immune response that have recently emerged as crucial controllers of tissue homeostasis. In particular, the nucleotide-binding domain, leucine-rich-containing (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a complex platform involved in the activation of caspase-1 and the maturation of interleukin (IL)-1β and IL-18, which are mainly released via pyroptosis. Pyroptosis is a caspase-1-dependent type of cell death that is mediated by the cl...
#1Yan Jiao (Dalian Medical University)H-Index: 1
#2Dandan Zhao (Dalian Medical University)H-Index: 3
Last. Ying Gao (Dalian Medical University)H-Index: 10
view all 11 authors...
Endothelial injury, which can cause endothelial inflammation and dysfunction, is an important mechanism for the development of atherosclerotic plaque. This study aims to investigate the functional role of miR-520c-3p in vascular endothelium during inflammatory diseases such as atherosclerosis. Quantitative real-time PCR was used to detect miR-520c-3p expression in in human umbilical vein endothelial cells (HUVECs) after treatment with platelet-derived growth factor (PDGF). Furthermore, the effec...
#1Yvonne Alexander (MMU: Manchester Metropolitan University)H-Index: 3
#2Elena Osto (ETH Zurich)H-Index: 20
Last. Paul C. Evans (University of Sheffield)H-Index: 52
view all 25 authors...
Endothelial cells (EC) are sentinels of cardiovascular health. Their function is reduced by the presence of cardiovascular risk factors, and is regained once pathological stimuli are removed. In this European Society for Cardiology Position Paper we describe endothelial dysfunction as a spectrum of phenotypic states and advocate further studies to determine the role of EC subtypes in cardiovascular disease. We conclude that there is no single ideal method for measurement of endothelial function....
#1Yang Li (Capital Medical University)H-Index: 4
#2Han YanH-Index: 7
Last. Xiao-Li Tian (PKU: Peking University)H-Index: 26
view all 8 authors...
AIMS: Genetic contribution to coronary artery disease (CAD) remains largely unillustrated. Although transcriptomic profiles have identified dozens of genes that are differentially expressed in normal and atherosclerotic vessels, whether those genes are genetically associated with CAD remains to be determined. Here, we combined genetic association studies, transcriptome profiles and in vitro and in vivo functional experiments to identify novel susceptibility genes for CAD. METHODS AND RESULTS: Th...
Cited By1
#1Panagiotis Theofilis (UoA: National and Kapodistrian University of Athens)H-Index: 5
#2Marios Sagris (UoA: National and Kapodistrian University of Athens)H-Index: 5
Last. Dimitris Tousoulis (UoA: National and Kapodistrian University of Athens)H-Index: 47
view all 6 authors...
Background: Atherosclerotic cardiovascular diseases are characterized by a dysregulated inflammatory and thrombotic state, leading to devastating complications with increased morbidity and mortality rates. Summary: In this review article, we present the available evidence regarding the impact of inflammation on platelet activation in atherosclerosis. Key messages: In the context of a dysfunctional vascular endothelium, structural alterations by means of endothelial glycocalyx thinning or functio...
#1Andreas Schmid (University of Giessen)H-Index: 11
#2Ann-Kathrin Vlacil (University of Marburg)H-Index: 5
Last. Karsten Grote (University of Marburg)H-Index: 27
view all 0 authors...
The C1q/TNF-related protein 3 (CTRP3) represents a pleiotropic adipokine reciprocally associated with obesity and type 2 diabetes mellitus and exhibits anti-inflammatory properties in relation to lipopolysaccharides (LPS)-mediated effects in adipocytes, as well as monocytes/macrophages. Here, we focused on the influence of CTRP3 on LPS-mediated effects in endothelial cells in order to expand the understanding of a possible anti-inflammatory function of CTRP3 in a setting of endotoxemia. An organ...
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