Immune checkpoint programmed death-1 mediates abdominal aortic aneurysm and pseudoaneurysm progression - 18/09/21


| pages | 9 |
| Iconographies | 7 |
| Vidéos | 0 |
| Autres | 0 |
Abstract |
Purpose |
The causes and pathogenetic mechanisms underlying abdominal aortic aneurysms (AAAs) and pseudoaneurysms are not fully understood. We hypothesized that inhibiting programmed death-1 (PD-1) can decrease AAA and pseudoaneurysm formation in mouse and rat models.
Methods |
Human AAA samples were examined in conjunction with an adventitial calcium chloride (CaCl2) application mouse model and an aortic patch angioplasty rat model. Single-dose PD-1 antibody (4 mg/kg) or BMS-1 (PD-1 inhibitor-1) (1 mg/kg) was administered by intraperitoneal (IP) or intraluminal injection. In the intramural injection group, PD-1 antibody was injected after CaCl2 incubation. The rats were divided into three groups: (1) the control group was only decellularized without other special treatment, (2) the PD-1 antibody-coated patch group, and (3) the BMS-1 coated patch group. Patches implanted in the rat abdominal aorta were harvested on day 14 after implantation and analyzed.
Results |
Immunohistochemical analysis showed PD-1–positive cells, PD-1 and CD3, PD-1 and CD68, and PD-1 and α-actin co-expressed in the human AAA samples. Intraperitoneal (IP) injection or intraluminal injection of PD-1antibody/BMS-1 significantly inhibited AAA progression. PD-1 antibody and BMS-1 were each successfully conjugated to decellularized rat thoracic artery patches, respectively, by hyaluronic acid. Patches coated with either humanized PD-1 antibody or BMS-1 can also inhibit pseudoaneurysm progression and inflammatory cell infiltration.
Conclusion |
PD-1 pathway inhibition may be a promising therapeutic strategy for inhibiting AAA and pseudoaneurysm progression.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Immune checkpoints may play a role in cardiovascular disease. |
• | PD-1 inhibits abdominal aortic aneurysms and pseudoaneurysms in rodents. |
Abbreviations : CD, DAB, DAPI, H&E, HRP, HA, IP, PD-1, PCNA, PBS, PD-L1, SD, TA, IHC, , IF, ANOVA, EVG
Keywords : Programmed death-1, Aortic aneurysm, Pseudoaneurysm, Lymphocyte, Intraluminal injection
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Vol 142
Article 111955- octobre 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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