Cigarette Tar Enhanced ECs Pyroptosis via CAMKII/Drp1/mtDNA: Novel Insight Into the Mechanism of Plaque Erosion

Xing Luo; Ji Li; Yuwu Chen; Xiuzhu Weng; Xiaoyi Bao; Xiaoxuan Bai; Ying Lv; Shan Zhang; Xinxin Zhu; Biyi Xu; Chen Zhao; Ming Zeng; Tianyu Wu; Qianhui Sun; Shengfang Wang; Minghao Liu; Thomas Johnson; Stephen J White; Peter Libby; Sining Hu; Bo Yu; Haibo Jia

doi:10.1016/j.jacbts.2025.03.015

Cigarette Tar Enhanced ECs Pyroptosis via CAMKII/Drp1/mtDNA: Novel Insight Into the Mechanism of Plaque Erosion

Xing Luo^*
, Ji Li^*
, Yuwu Chen
, Xiuzhu Weng
, Xiaoyi Bao
, Xiaoxuan Bai
, Ying Lv
, Shan Zhang
, Xinxin Zhu
, Biyi Xu
, Chen Zhao
, Ming Zeng
, Tianyu Wu
, Qianhui Sun
, Shengfang Wang
, Minghao Liu
, Thomas Johnson
, Stephen J White
, Peter Libby
, Sining Hu

Bo Yu, Haibo Jia

^*Corresponding author for this work

Bristol Medical School (THS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

4 Citations (Scopus)

Abstract

Smoking is the only cardiovascular risk factor for plaque erosion. We found cigarette tar resulted in erosion-like lesion development in apolipoprotein E^-/- mice, with mural thrombosis, discontinuous endothelium, platelet activation, smooth muscle cell proliferation, and hyaluronic acid accumulation in the aorta. Single-cell transcriptomics revealed that genes relating to pyroptosis, platelet activation, and leukocytes adhesion were significantly increased in an endothelial cell subset. Rescue assays indicated cigarette tar caused human coronary artery endothelial cell pyroptosis by enhanced calcium-calmodulin-dependent protein kinase II / dynamin-related protein 1-mediated mitochondrial fission and mitochondrial DNA release via activating Ca²⁺ signaling. Inhibition of endothelial cell pyroptosis may be a novel therapeutic strategy to reduce plaque erosion.

Original language	English
Article number	101283
Number of pages	18
Journal	JACC: Basic to Translational Science
Volume	10
Issue number	8
DOIs	https://doi.org/10.1016/j.jacbts.2025.03.015
Publication status	Published - 25 Aug 2025

Bibliographical note

Publisher Copyright:
© 2025. Published by Elsevier on Behalf of The American College of Cardiology Foundation

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Luo, X., Li, J., Chen, Y., Weng, X., Bao, X., Bai, X., Lv, Y., Zhang, S., Zhu, X., Xu, B., Zhao, C., Zeng, M., Wu, T., Sun, Q., Wang, S., Liu, M., Johnson, T., White, S. J., Libby, P., ... Jia, H. (2025). Cigarette Tar Enhanced ECs Pyroptosis via CAMKII/Drp1/mtDNA: Novel Insight Into the Mechanism of Plaque Erosion. JACC: Basic to Translational Science, 10(8), Article 101283. https://doi.org/10.1016/j.jacbts.2025.03.015

@article{8452ef5d6e9e41c893470d3679c503d8,

title = "Cigarette Tar Enhanced ECs Pyroptosis via CAMKII/Drp1/mtDNA: Novel Insight Into the Mechanism of Plaque Erosion",

abstract = "Smoking is the only cardiovascular risk factor for plaque erosion. We found cigarette tar resulted in erosion-like lesion development in apolipoprotein E -/- mice, with mural thrombosis, discontinuous endothelium, platelet activation, smooth muscle cell proliferation, and hyaluronic acid accumulation in the aorta. Single-cell transcriptomics revealed that genes relating to pyroptosis, platelet activation, and leukocytes adhesion were significantly increased in an endothelial cell subset. Rescue assays indicated cigarette tar caused human coronary artery endothelial cell pyroptosis by enhanced calcium-calmodulin-dependent protein kinase II / dynamin-related protein 1-mediated mitochondrial fission and mitochondrial DNA release via activating Ca 2+ signaling. Inhibition of endothelial cell pyroptosis may be a novel therapeutic strategy to reduce plaque erosion. ",

author = "Xing Luo and Ji Li and Yuwu Chen and Xiuzhu Weng and Xiaoyi Bao and Xiaoxuan Bai and Ying Lv and Shan Zhang and Xinxin Zhu and Biyi Xu and Chen Zhao and Ming Zeng and Tianyu Wu and Qianhui Sun and Shengfang Wang and Minghao Liu and Thomas Johnson and White, \{Stephen J\} and Peter Libby and Sining Hu and Bo Yu and Haibo Jia",

note = "Publisher Copyright: {\textcopyright} 2025. Published by Elsevier on Behalf of The American College of Cardiology Foundation",

year = "2025",

month = aug,

day = "25",

doi = "10.1016/j.jacbts.2025.03.015",

language = "English",

volume = "10",

journal = "JACC: Basic to Translational Science",

issn = "2452-302X",

publisher = "Elsevier Inc.",

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Luo, X, Li, J, Chen, Y, Weng, X, Bao, X, Bai, X, Lv, Y, Zhang, S, Zhu, X, Xu, B, Zhao, C, Zeng, M, Wu, T, Sun, Q, Wang, S, Liu, M, Johnson, T, White, SJ, Libby, P, Hu, S, Yu, B & Jia, H 2025, 'Cigarette Tar Enhanced ECs Pyroptosis via CAMKII/Drp1/mtDNA: Novel Insight Into the Mechanism of Plaque Erosion', JACC: Basic to Translational Science, vol. 10, no. 8, 101283. https://doi.org/10.1016/j.jacbts.2025.03.015

TY - JOUR

T1 - Cigarette Tar Enhanced ECs Pyroptosis via CAMKII/Drp1/mtDNA

T2 - Novel Insight Into the Mechanism of Plaque Erosion

AU - Luo, Xing

AU - Li, Ji

AU - Chen, Yuwu

AU - Weng, Xiuzhu

AU - Bao, Xiaoyi

AU - Bai, Xiaoxuan

AU - Lv, Ying

AU - Zhang, Shan

AU - Zhu, Xinxin

AU - Xu, Biyi

AU - Zhao, Chen

AU - Zeng, Ming

AU - Wu, Tianyu

AU - Sun, Qianhui

AU - Wang, Shengfang

AU - Liu, Minghao

AU - Johnson, Thomas

AU - White, Stephen J

AU - Libby, Peter

AU - Hu, Sining

AU - Yu, Bo

AU - Jia, Haibo

PY - 2025/8/25

Y1 - 2025/8/25

N2 - Smoking is the only cardiovascular risk factor for plaque erosion. We found cigarette tar resulted in erosion-like lesion development in apolipoprotein E -/- mice, with mural thrombosis, discontinuous endothelium, platelet activation, smooth muscle cell proliferation, and hyaluronic acid accumulation in the aorta. Single-cell transcriptomics revealed that genes relating to pyroptosis, platelet activation, and leukocytes adhesion were significantly increased in an endothelial cell subset. Rescue assays indicated cigarette tar caused human coronary artery endothelial cell pyroptosis by enhanced calcium-calmodulin-dependent protein kinase II / dynamin-related protein 1-mediated mitochondrial fission and mitochondrial DNA release via activating Ca 2+ signaling. Inhibition of endothelial cell pyroptosis may be a novel therapeutic strategy to reduce plaque erosion.

AB - Smoking is the only cardiovascular risk factor for plaque erosion. We found cigarette tar resulted in erosion-like lesion development in apolipoprotein E -/- mice, with mural thrombosis, discontinuous endothelium, platelet activation, smooth muscle cell proliferation, and hyaluronic acid accumulation in the aorta. Single-cell transcriptomics revealed that genes relating to pyroptosis, platelet activation, and leukocytes adhesion were significantly increased in an endothelial cell subset. Rescue assays indicated cigarette tar caused human coronary artery endothelial cell pyroptosis by enhanced calcium-calmodulin-dependent protein kinase II / dynamin-related protein 1-mediated mitochondrial fission and mitochondrial DNA release via activating Ca 2+ signaling. Inhibition of endothelial cell pyroptosis may be a novel therapeutic strategy to reduce plaque erosion.

U2 - 10.1016/j.jacbts.2025.03.015

DO - 10.1016/j.jacbts.2025.03.015

M3 - Article (Academic Journal)

C2 - 40866045

SN - 2452-302X

VL - 10

JO - JACC: Basic to Translational Science

JF - JACC: Basic to Translational Science

IS - 8

M1 - 101283

ER -

Cigarette Tar Enhanced ECs Pyroptosis via CAMKII/Drp1/mtDNA: Novel Insight Into the Mechanism of Plaque Erosion

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