Vascular Endothelium

Physiology

  • It regulates the vascular tone, the adhesion of inflammatory cells, it participates in hemostasis and in angiogenesis, among other functions.
  • It has the ability to adapt to the different stimuli present in circulation. When this ability is lost due to a persistent stimulus, it may become dysfunctional.

Normal Endothelium

Endothelial injury repair

Monocytes on dysfunctional Endothelium

Endothelial dysfunction

  • Dysregulation of the physiological functions of the vascular endothelium, resulting in reduced vasodilating capacity, enhanced proinflammatory and prothrombotic properties, and abnormal modulation of vascular smooth muscle cell growth and migration.
  • Common characteristic in many diseases, such as chronic kidney disease, obesity, diabetes, major depression, septic syndromes, and COVID-19, and also certain treatments, such as hematopoietic stem cell transplantation.

Chronic Kidney Disease (CKD)

  • Accelerated atherosclerosis, increased risk of thrombotic-ischemic complications, and excessive mortality rates when compared with the general population.
  • Different factors causing endothelial damage: accumulation of toxins, due to reduced renal clearance, activation of cells through the dialysis filters, activation of the innate immunity.

Hematopoietic stem cell transplantation (HCT)

  • Hematopoietic stem cell transplantation (HCT) is the only curative treatment option for many patients suffering from hematological malignancies.
  • There are complications that appear early after HCT, which have the endothelial damage and activation as the main pathophysiological substrate.
  • Endothelial cells develop a pro-inflammatory and prothrombotic phenotype, due to the effect of conditioning treatment, the engraftment and allogenicity.

COVID-19

  • Patients with COVID-19 present a wide spectrum of disease severity, from asymptomatic cases to serious disease leading to critical care and even death.
  • Levels of some markers of endothelial activation and damage are associated with the disease severity.

Micrographs showing immunofluorescence detection of ICAM-1 (left image) and VCAM-1 (right image) on the surface of endothelial cells after being exposed to a damaging condition.

Bibliography

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Escolar G, Diaz-Ricart M, Cases A. Uremic platelet dysfunction: past and present. Curr Hematol Rep. 2005; 4: 359-67.

Diaz-Ricart M, Carmona A, Palomo M, Rovira M, Escolar G, Carreras E. Impact of Different Immunosuppresive Drugs on the Endothelium. Protective Effect of Defibrotide. ASH Annual Meeting Abstracts. 2011; 118: 5319.

Palomo M, Mir E, Rovira M, Escolar G, Carreras E, Diaz-Ricart M. What is going on between defibrotide and endothelial cells? Snapshots reveal the hot spots of their romance. Blood. 2016; 127: 1719-27. 10.1182/blood-2015-10-676114.

Martinez-Sanchez J, Palomo M, Torramade-Moix S, Moreno-Castano AB, Rovira M, Gutierrez-Garcia G, Fernandez-Aviles F, Escolar G, Penack O, Rosinol L, Carreras E, Diaz-Ricart M. The induction strategies administered in the treatment of multiple myeloma exhibit a deleterious effect on the endothelium. Bone Marrow Transplant. 2020; 55: 2270-8. 10.1038/s41409-020-0947-9.

Palomo M, Diaz-Ricart M, Carbo C, Rovira M, Fernandez-Aviles F, Martine C, Ghita G, Escolar G, Carreras E. Endothelial dysfunction after hematopoietic stem cell transplantation: role of the conditioning regimen and the type of transplantation. Biol Blood Marrow Transplant. 2010; 16: 985-93. 10.1016/j.bbmt.2010.02.008.

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Torramade-Moix S, Palomo M, Vera M, Jerez D, Moreno-Castano AB, Zafar MU, Rovira J, Diekmann F, Garcia-Pagan JC, Escolar G, Cases A, Diaz-Ricart M. Apixaban Downregulates Endothelial Inflammatory and Prothrombotic Phenotype in an In Vitro Model of Endothelial Dysfunction in Uremia. Cardiovasc Drugs Ther. 2021; 35: 521-32. 10.1007/s10557-020-07010-z.

Hanzu FA, Palomo M, Kalko SG, Parrizas M, Garaulet M, Escolar G, Gomis R, Diaz-Ricart M. Translational evidence of endothelial damage in obese individuals: inflammatory and prothrombotic responses. J Thromb Haemost. 2011; 9: 1236-45. 10.1111/j.1538-7836.2011.04285.x.

Castro P, Palomo M, Moreno-Castano AB, Fernandez S, Torramade-Moix S, Pascual G, Martinez-Sanchez J, Richardson E, Tellez A, Nicolas JM, Carreras E, Richardson PG, Badimon JJ, Escolar G, Diaz-Ricart M. Is the Endothelium the Missing Link in the Pathophysiology and Treatment of COVID-19 Complications? Cardiovasc Drugs Ther. 2021. 10.1007/s10557-021-07207-w.

Fernandez S, Moreno-Castano AB, Palomo M, Martinez-Sanchez J, Torramade-Moix S, Tellez A, Ventosa H, Segui F, Escolar G, Carreras E, Nicolas JM, Richardson E, Garcia-Bernal D, Carlo-Stella C, Moraleda JM, Richardson PG, Diaz-Ricart M, Castro P. Distinctive Biomarker Features in the Endotheliopathy of COVID-19 and Septic Syndromes. Shock. 2022; 57: 95-105. 10.1097/SHK.0000000000001823.