Immune checkpoint programmed death-1 mediates abdominal aortic aneurysm and pseudoaneurysm progression

  • Biomed Pharmacother. 2021 Oct;142:111955. doi: 10.1016/j.biopha.2021.111955.
Peng Sun  1 ,  Liwei Zhang  1 ,  Yulei Gu  2 ,  Shunbo Wei  1 ,  Zhiwei Wang  1 ,  Mingxing Li  1 ,  Wang Wang  3 ,  Zhiju Wang  4 ,  Hualong Bai  5
Affiliations
  • 1. Department of Vascular and Endovascular Surgery, First Affiliated Hospital of Zhengzhou University, 450052 Henan, China.
  • 2. Emergency Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, 450052 Henan, China.
  • 3. Key Vascular Physiology and Applied Research Laboratory of Zhengzhou City, 450002 Henan, China; Department of Physiology, Medical School of Zhengzhou University, 450002 Henan, China.
  • 4. Department of Physiology, Medical School of Zhengzhou University, 450002 Henan, China.
  • 5. Department of Vascular and Endovascular Surgery, First Affiliated Hospital of Zhengzhou University, 450052 Henan, China; Key Vascular Physiology and Applied Research Laboratory of Zhengzhou City, 450002 Henan, China. Electronic address: [email protected].
PMID: 34339918 DOI: 10.1016/j.biopha.2021.111955
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.

Keywords
Aortic aneurysm; Intraluminal injection; Lymphocyte; Programmed death-1; Pseudoaneurysm.
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