Putting function back in dysfunction: Endothelial diseases and current therapies in hematopoietic stem cell transplantation and cellular therapies. (January 2022)

• Record Type: Journal Article
• Authors: Sumransub, Nuttavut; El Jurdi, Najla; Chiraphapphaiboon, Wannasiri; Maakaron, Joseph E.
• Is Part Of: Blood reviews. Volume 51(2022)
• Publication Date: 2022-01
• Subjects: Endothelial dysfunction -- Graft-versus-host disease -- CAR-T cell -- Cytokine release syndrome (CRS) -- Neurotoxicity -- Immune effector cell associated neurotoxicity (ICANS) -- CAR-T cell-related encephalopathy syndrome (CRES) -- HMG-CoA reductase inhibitors -- Defibrotide -- Recombinant thrombomodulin; ADAMTS-13 A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 -- Ang Angiopoietin -- AP-1 Activator protein 1 -- AT-II Angiotensin-II -- BBB Blood-brain barrier -- CAR Chimeric antigen receptor -- CCl Chemokine ligand -- CD Cluster of differentiation -- CEC Circulating endothelial cells -- CKD Chronic kidney disease -- CLS Capillary leak syndrome -- COVID-19 Coronavirus disease 2019 -- COX Cyclooxygenase -- CRES CAR T-cell related encephalopathy syndrome -- CRS Cytokine release syndrome -- CSF Cerebrospinal fluid -- DAMP Damage-associated molecular pattern -- DIC Disseminated intravascular coagulation -- DNA Deoxyribonucleic acid -- EASIX Endothelial activation and stress index -- ES Engraftment syndrome -- ESAM Endothelial cell-selective adhesion molecule -- ET-1 Endothelin-1 -- FOXP3 Forkhead box P3 -- FS Follistatin -- G-CSF Granulocyte colony stimulating factor -- GPCR G-protein coupled receptor -- GTP Guanosine triphosphate -- GVHD Graft-versus-host disease -- GVL Graft-versus-leukemia -- HCT Hematopoietic stem cell transplantation -- HGF Hepatocyte growth factor -- HLA Human leukocyte antigen -- HMG-CoA 3-hydroxy 3-methyl-glutaryl-coenzyme A -- HUS Hemolytic uremic syndrome -- ICAM Endothelial intercellular adhesion molecule -- ICANS Immune Effector Cell Associated Neurotoxicity -- IL Interleukin -- IPS Idiopathic pneumonia syndrome -- JAM Junctional adhesion molecules -- KLF Kruppel-like factor -- LFA-1 Lymphocyte function-associated antigen -- MCP-1 Monocyte chemoattractant protein-1 -- MHC Major histocompatibility complex -- MOD Multi-organ dysfunction -- NADPH Nicotinamide adenine dinucleotide phosphate -- NF-kB Nuclear factor kappa-light-chain-enhancer of activated B cells -- NO Nitric oxide -- NOS Nitric oxide synthase -- NRM Non-relapse mortality -- OS Overall survival -- PAI-1 Plasminogen activator inhibitor type-1 -- PECAM-1 Platelet/endothelial cell adhesion molecule -- PFS Progression-free survival -- PGE2 Prostaglandin E2 -- PGI2 Prostacyclin -- PlGF Placental growth factor -- PPAR Peroxisome proliferator-activated receptor -- PSGL P-selectin glycoprotein ligand -- Rho Ras-homolog protein -- ROCK Rho-associated protein kinase -- rTM Recombinant thrombomodulin -- sTM Soluble thrombomodulin -- TA-TMA Transplant-associated thrombotic microangiopathy -- TF Tissue factor -- TGF-β Transforming growth factor-beta -- Th Helper T cell -- TNF Tumor necrosis factor -- tPA Tissue plasminogen activator -- Tregs Regulatory T cells -- VCAM Vascular cell adhesion molecule -- VEGF Vascular endothelial growth factor -- VOD/SOS Veno-occlusive disease/sinusoidal obstruction syndrome -- VSMC Vascular smooth muscles; Hematology -- Periodicals; Hematology -- Periodicals; Hématologie -- Périodiques; Hematology; Electronic journals; Periodicals; 616.15
• DOI: 10.1016/j.blre.2021.100883
• Languages: English
• ISSNs: 0268-960X

Abstract

Abstract: Endothelial dysfunction is characterized by altered vascular permeability and prothrombotic, pro-inflammatory phenotypes. Endothelial dysfunction results in end-organ damage and has been associated with diverse disease pathologies. Complications observed after hematopoietic stem cell transplantation (HCT) and chimeric antigen receptor-T cell (CAR-T) therapy for hematologic and neoplastic disorders share overlapping clinical manifestations and there is increasing evidence linking these complications to endothelial dysfunction. Despite advances in supportive care and treatments, end-organ toxicity remains the leading cause of mortality. A new strategy to mitigate endothelial dysfunction could lead to improvement of clinical outcomes for patients. Statins have demonstrated pleiotropic effects of immunomodulatory and endothelial protection by various molecular mechanisms. Recent applications in immune-mediated diseases such as autoimmune disorders, chronic inflammatory conditions, and graft-versus-host disease (GVHD) have shown promising results. In this review, we cover the mechanisms underlying endothelial dysfunction in GVHD and CAR-T cell-related toxicities. We summarize the current knowledge about statins and other agents used as endothelial protectants. We propose further studies using statins for prophylaxis and prevention of end-organ damage related to extensive endothelial dysfunction in HCT and CAR-T.