Inflammatory Mechanisms Contributing to Endothelial Dysfunction
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 inflammat...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/9/7/781 |
| _version_ | 1797527627558289408 |
|---|---|
| author | Panagiotis Theofilis Marios Sagris Evangelos Oikonomou Alexios S. Antonopoulos Gerasimos Siasos Costas Tsioufis Dimitris Tousoulis |
| author_facet | Panagiotis Theofilis Marios Sagris Evangelos Oikonomou Alexios S. Antonopoulos Gerasimos Siasos Costas Tsioufis Dimitris Tousoulis |
| author_sort | Panagiotis Theofilis |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T09:45:29Z |
| format | Article |
| id | doaj.art-e4668963614346ac8ebed71fe0522984 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T09:45:29Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-e4668963614346ac8ebed71fe05229842023-11-22T03:16:54ZengMDPI AGBiomedicines2227-90592021-07-019778110.3390/biomedicines9070781Inflammatory Mechanisms Contributing to Endothelial DysfunctionPanagiotis Theofilis0Marios Sagris1Evangelos Oikonomou2Alexios S. Antonopoulos3Gerasimos Siasos4Costas Tsioufis5Dimitris Tousoulis61st Department of Cardiology, Hippokration General Hospital, University of Athens Medical School, 11527 Athens, Greece1st Department of Cardiology, Hippokration General Hospital, University of Athens Medical School, 11527 Athens, Greece1st Department of Cardiology, Hippokration General Hospital, University of Athens Medical School, 11527 Athens, Greece1st Department of Cardiology, Hippokration General Hospital, University of Athens Medical School, 11527 Athens, Greece1st Department of Cardiology, Hippokration General Hospital, University of Athens Medical School, 11527 Athens, Greece1st Department of Cardiology, Hippokration General Hospital, University of Athens Medical School, 11527 Athens, Greece1st Department of Cardiology, Hippokration General Hospital, University of Athens Medical School, 11527 Athens, GreeceMaintenance 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.https://www.mdpi.com/2227-9059/9/7/781endothelial dysfunctioninflammationNf-κBadhesion moleculesselectinsNLRP3 inflammasome |
| spellingShingle | Panagiotis Theofilis Marios Sagris Evangelos Oikonomou Alexios S. Antonopoulos Gerasimos Siasos Costas Tsioufis Dimitris Tousoulis Inflammatory Mechanisms Contributing to Endothelial Dysfunction Biomedicines endothelial dysfunction inflammation Nf-κB adhesion molecules selectins NLRP3 inflammasome |
| title | Inflammatory Mechanisms Contributing to Endothelial Dysfunction |
| title_full | Inflammatory Mechanisms Contributing to Endothelial Dysfunction |
| title_fullStr | Inflammatory Mechanisms Contributing to Endothelial Dysfunction |
| title_full_unstemmed | Inflammatory Mechanisms Contributing to Endothelial Dysfunction |
| title_short | Inflammatory Mechanisms Contributing to Endothelial Dysfunction |
| title_sort | inflammatory mechanisms contributing to endothelial dysfunction |
| topic | endothelial dysfunction inflammation Nf-κB adhesion molecules selectins NLRP3 inflammasome |
| url | https://www.mdpi.com/2227-9059/9/7/781 |
| work_keys_str_mv | AT panagiotistheofilis inflammatorymechanismscontributingtoendothelialdysfunction AT mariossagris inflammatorymechanismscontributingtoendothelialdysfunction AT evangelosoikonomou inflammatorymechanismscontributingtoendothelialdysfunction AT alexiossantonopoulos inflammatorymechanismscontributingtoendothelialdysfunction AT gerasimossiasos inflammatorymechanismscontributingtoendothelialdysfunction AT costastsioufis inflammatorymechanismscontributingtoendothelialdysfunction AT dimitristousoulis inflammatorymechanismscontributingtoendothelialdysfunction |