title: 5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Inhibits RIPK1/RIPK3-Dependent Necroptosis in THP-1-Derived Foam Cells.
abstract: Necroptosis, or programmed necrosis, contributes to the formation of necrotic cores in atherosclerotic plaque in animal models. However, whether inhibition of necroptosis ameliorates atherosclerosis is largely unknown. In this study, we demonstrated that necroptosis occurred in clinical atherosclerotic samples, suggesting that it may also play an important role in human atherosclerosis. We established an in vitro necroptotic model in which necroptosis was induced in THP-1-derived foam cells by serum deprivation. With this model, we demonstrated that 5-aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) inhibited necroptosis while promoting apoptosis. ALA-SDT activated the caspase-3 and caspase-8 pathways in foam cells, which is responsible for the switch from necroptosis to apoptosis. The inhibition of either caspase-8 or caspase-3 abolished the anti-necroptotic effect of ALA-SDT. In addition, we found that caspase-3 activation peaked 4 hours after ALA-SDT treatment, 2 hours earlier than maximal caspase-8activation. Taken together, our data indicate that ALA-SDT mediates the switch from necroptosis to apoptosis by activating the caspase-3 and caspase-8 pathways and may improve the prognosis of atherosclerosis.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, 150001, P. R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, 150001, P. R. China.
authors.forename: Jianting
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Pathophysiology and the Key Laboratory of Cardiovascular Pathophysiology, Harbin Medical University, the Key Laboratory of Cardiovascular Research (Harbin Medical University), Ministry of Education, Harbin 150081, P. R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yan
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, 150001, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, 150001, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, 150001, P. R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Pathophysiology and the Key Laboratory of Cardiovascular Pathophysiology, Harbin Medical University, the Key Laboratory of Cardiovascular Research (Harbin Medical University), Ministry of Education, Harbin 150081, P. R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, 150001, P. R. China.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, 150001, P. R. China.
authors.forename: Zengxiang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, 150001, P. R. China.
authors.forename: Bicheng
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Forensic Medicine, Harbin Medical University, Harbin 150001, P. R. China.
authors.forename: Tielei
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Vascular Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Shan
authors.affiliation: Department of Vascular Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Vascular Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, 150001, P. R. China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, 150001, P. R. China.
authors.forename: Qianping
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Laboratory of Photo- and Sono-theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin 150080, P. R. China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Laboratory of Photo- and Sono-theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin 150080, P. R. China.|Materials Research Institute, The Pennsylvania State University, University Park 16802, PA, USA.
authors.forename: Wenwu
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, 150001, P. R. China.|Department of Pathophysiology and the Key Laboratory of Cardiovascular Pathophysiology, Harbin Medical University, the Key Laboratory of Cardiovascular Research (Harbin Medical University), Ministry of Education, Harbin 150081, P. R. China.|Heilongjiang Academy of Medical Sciences, Harbin 150086, P. R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D005487:Foam Cells / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D009336:Necrosis; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism*; D000069453:Ultrasonic Waves
chemical_list: D007093:Imidazoles; D007211:Indoles; C507699:necrostatin-1; D000622:Aminolevulinic Acid; C506249:RIPK1 protein, human; C119705:RIPK3 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D053148:Caspase 3; D053181:Caspase 8