DAPK1 may be a potential biomarker for arterial aneurysm in clinical treatment and activated inflammation levels in arterial aneurysm through NLRP3 inflammasome by Beclin1.

Abstract

BACKGROUND:

Death-associated protein kinase (DAPK1) is one of the positive regulators of apoptosis, and it is widely involved in apoptosis induced by multiple pathways. We examined that the function of DAPK1 in Clinical treatment of arterial aneurysm and its underlying mechanisms. Arterial aneurysm is a common cerebrovascular disease with high disability and fatality rate.

OBJECTIVES:

Male C57BL/6 mice or DAPK1-/- mice were injected with 50 mg/kg pentobarbital sodium and then were injected with angiotensin II (AngII) infusion for vivo model. hASMCs (Human artery smooth muscle cell) were treated with murine recombinant IL-6 (20  ng ml-1; Cell Signaling) for vitro model.

RESULTS:

DAPK1 gene, mRNA expression, and protein expression were induced in mice of arterial aneurysm. DAPK1 mRNA expression was increased and Area Under Curve was 0.9075 in patients with arterial aneurysm. Knockout of DAPK1 decreased inflammation and vascular injury in mice model of arterial aneurysm. Beclin1/NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) signal pathway is a critical downstream effector of DAPK1 by TAP production. The regulation of Beclin1 participated in the effects of DAPK1 on inflammation of arterial aneurysm by ATP-dependent NLRP3 inflammasome. The regulation of NLRP3 participated in the effects of DAPK1 on inflammation of arterial aneurysm.

CONCLUSION:

Collectively, our data indicated that DAPK1 may be a potential biomarker for arterial aneurysm in clinical treatment and activated inflammation levels in arterial aneurysm through NLRP3 inflammasome by Beclin1. DAPK1 might be a key pathogenic event underlying excess inflammation of arterial aneurysm.

• Authors: Senyan Wu, Wei Lu, Guobing Cheng, Jiawen Wu, Sheng Liao, Qiang Hu, Xiaoyang Li, Buping Jiang
• Journal: Human & experimental toxicology (Hum Exp Toxicol) Vol. 40 Issue 12_suppl Pg. S563-S572 (Dec 2021) ISSN: 1477-0903 [Electronic] England
• PMID: 34796763 (Publication Type: Journal Article)

Chemical References

• Beclin-1
• Biomarkers
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Dapk1 protein, mouse
• Death-Associated Protein Kinases

Topics

• Adult
• Aneurysm (metabolism)
• Animals
• Beclin-1 (metabolism)
• Biomarkers (metabolism)
• Death-Associated Protein Kinases (genetics, metabolism)
• Female
• Humans
• Inflammasomes (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Middle Aged
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)