scholarly journals Endothelial-immune crosstalk contributes to vasculopathy in non-alcoholic fatty liver disease

2021 ◽  
Author(s):  
Chun-Yi Ng ◽  
Khang Leng Lee ◽  
Mark Dhinesh Muthiah ◽  
Kan Xing Wu ◽  
Florence Chioh ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Single Cell Analysis ◽  
Human Leukocyte ◽  
Cardiovascular Complications ◽  
Alcoholic Fatty Liver ◽  
Leukocyte Antigens ◽  
Alcoholic Fatty Liver Disease

The top cause of mortality in patients with non-alcoholic fatty liver disease (NAFLD) is cardiovascular complications. However, the mechanisms of NAFLD-associated vasculopathy remain understudied. We developed blood outgrowth endothelial cell (BOEC) models from NAFLD and healthy subjects. NAFLD BOECs exhibited global transcriptional upregulation of chemokine hallmarks and human leukocyte antigens. In mouse models of diet-induced NAFLD, we further confirmed enhanced endothelial expressions of CXCL12 in the aortas and liver vasculatures. To elucidate endothelial-immune crosstalk, we performed immunoprofiling by single-cell analysis, uncovering T cell intensification and potentially T-helper type 1 inflammation in NAFLD patients. Functionally, interference of the CXCL12-CXCR4 axis by small molecule AMD3100 selectively modulated the chemotaxis of patient-derived CD4+ T cells and natural killer cells towards NAFLD BOECs, restoring endothelial barrier integrity. Clinically, we detected three folds more circulating damaged endothelial cells in NAFLD patients than healthy controls. Our work provides insights for modulation of interactions with effector immune subsets to mitigate endothelial injury in NAFLD.

scholarly journals Features of the therapy of non-alcoholic fatty liver disease in comorbid patients

2021 ◽  
pp. 136-143
Author(s):  
M. M. Maevskaya
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Modern Society ◽  
Cardiovascular Complications ◽  
Efficacy And Safety ◽  
Alcoholic Fatty Liver ◽  
Positive Effect ◽  
Alcoholic Fatty Liver Disease

The problem of modern medicine and modern society is a comorbid patient with metabolic disorders. Hypothetical portrait of such a patient: over 40 years old, overweight, arterial hypertension, coronary atherosclerosis, impaired carbohydrate and lipid metabolism, liver steatosis or steato-hepatitis, often with changes in the function of the musculoskeletal system. Rational pharmacotherapy of this patient is of fundamental importance. The article analyzes, from the point of view of polypotency, efficacy and safety, the main drugs used in Russia for treatment of non-alcoholic fatty liver disease in comorbid patients. Attention is paid to vitamin E, glycyrrhizin, ursodeoxycholic acid. Domestic and foreign studies of these drugs are analyzed, and the scope of their rational use is shown: reducing the risk of cardiovascular complications, a positive effect on the lipid spectrum, reducing the activity of serum transaminases and other hepatotropic effects. Their side effects are also considered, which should be taken into account when choosing the treatment of a comorbid patient. We have analyzed the efficacy and safety of new molecules that are in clinical trials and/or have not yet been registered in our country, e.g. obeticholic acid, cenicriviroc, tropifexor, etc. The ability of some molecules to act as biological enhancers is also highlighted, which is important to consider when prescribing combination therapy. Doctors are recommended to carefully consider and take into account all the features of a comorbid patient and choose for this category of patients safe drugs of hepatotropic action with simultaneous positive effect on the cardiovascular system. Among other things, it will avoid polypragmasy.

scholarly journals Type 1 Diabetes and Non-Alcoholic Fatty Liver Disease: When Should We Be Concerned? A Nationwide Study in Brazil

Nutrients ◽  
2017 ◽  
Vol 9 (8) ◽  
pp. 878 ◽  
Author(s):  
Bianca Barros ◽  
Deborah Conte Santos ◽  
Marcela Haas Pizarro ◽  
Laura Melo ◽  
Marilia Brito Gomes
Keyword(s):  
Type 1 Diabetes ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Nationwide Study ◽  
Alcoholic Fatty Liver Disease
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