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Review
. 2022 Jan 26;11(3):623.
doi: 10.3390/jcm11030623.

Endothelial Dysfunction after Hematopoietic Stem Cell Transplantation: A Review Based on Physiopathology

Giuseppe Milone  1 , Claudia Bellofiore  1 , Salvatore Leotta  1 , Giulio Antonio Milone  1 , Alessandra Cupri  1 , Andrea Duminuco  1 , Bruno Garibaldi  1 , Giuseppe Palumbo  1
Affiliations
Review

Endothelial Dysfunction after Hematopoietic Stem Cell Transplantation: A Review Based on Physiopathology

Giuseppe Milone et al. J Clin Med. .

Abstract

Endothelial dysfunction (ED) is frequently encountered in transplant medicine. ED is an argument of high complexity, and its understanding requires a wide spectrum of knowledge based on many fields of basic sciences such as molecular biology, immunology, and pathology. After hematopoietic stem cell transplantation (HSCT), ED participates in the pathogenesis of various complications such as sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), graft-versus-host disease (GVHD), transplant-associated thrombotic microangiopathy (TA-TMA), idiopathic pneumonia syndrome (IPS), capillary leak syndrome (CLS), and engraftment syndrome (ES). In the first part of the present manuscript, we briefly review some biological aspects of factors involved in ED: adhesion molecules, cytokines, Toll-like receptors, complement, angiopoietin-1, angiopoietin-2, thrombomodulin, high-mobility group B-1 protein, nitric oxide, glycocalyx, coagulation cascade. In the second part, we review the abnormalities of these factors found in the ED complications associated with HSCT. In the third part, a review of agents used in the treatment of ED after HSCT is presented.

Keywords: acute graft-versus-host disease; capillary leak syndrome; endothelial dysfunction; engraftment syndrome; idiopathic pneumonia syndrome; liver sinusoidal obstructive syndrome/veno-occlusive disease; transplant-associated thrombotic microangiopathy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The endothelial cells state results from the balance of various inflammatory/anti-inflammatory factors.
Figure 2
Figure 2
Pathogenic factor in endothelium-related complications after allogeneic hematopoietic stem cell transplantation.
Figure 3
Figure 3
Effects of TNF on endothelial cells.
Figure 4
Figure 4
Upon stimulation with TNF-α, endothelial cells’ signal transduction involves NF-κβ signaling associated with p38 MAPK.
Figure 5
Figure 5
The hypothesis of an auto-maintaining loop in EC activation.
Figure 6
Figure 6
Effects of HMGB-1 on endothelial cells.
Figure 7
Figure 7
The opposite effects of Ang-1 and Ang-2 on endothelium.
Figure 8
Figure 8
Antithrombotic and anti-inflammatory effects of thrombomodulin.
Figure 9
Figure 9
Abnormalities in alternative pathway of complement associated with TATMA.
Figure 10
Figure 10
Ang-2 and FAS-L in cortico-sensitive and corticosteroid-refractory a-GVHD.
See this image and copyright information in PMC

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