ReferenceID 1771
Dihydrotanshinone I Attenuates Plaque Vulnerability in Apolipoprotein E-Deficient Mice: Role of Receptor-Interacting Protein 3
Antioxid Redox Signal
Aims: Vulnerable plaque disruption in advanced atherosclerosis leads to acute thrombus and subsequent myocardial infarction and severely threatens human health. Necroptosis of macrophage involved in the necrotic core is
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- Reference Id
- 1771
- Evidence Id
- 18361
- Core Evidence Id
- 18361
- Source Reference Id
- 3529
- Herb2 Reference Id
- HBREF004326
- Subject Paper Key
- HBIN023994_32323566
- Pubmed Id
- 32323566
- Doi
- 10.1089/ars.2019.7796
- Paper Title
- Dihydrotanshinone I Attenuates Plaque Vulnerability in Apolipoprotein E-Deficient Mice: Role of Receptor-Interacting Protein 3
- Paper Abstract
- Aims: Vulnerable plaque disruption in advanced atherosclerosis leads to acute thrombus and subsequent myocardial infarction and severely threatens human health. Necroptosis of macrophage involved in the necrotic core is one key factor for plaque vulnerability. Dihydrotanshinone I (DHT) is a natural diterpenoid isolated from Danshen demonstrating effective anti-inflammatory property. It is accepted that inflammation plays a crucial role in the process of atherogenesis. However, whether DHT prevents atherosclerosis is poorly understood. Here, we investigated the effect of DHT on vulnerable plaque in an apolipoprotein E-deficient (ApoE-/-) mice model of atherosclerosis and the underlying protective mechanisms. Results: In the in vitro experiment, first LPS/ZVAD (LPS, lipopolysaccharide; ZVAD, ZVAD-FMK, a cell-permeable pan-caspase inhibitor) stimulated necroptosis of macrophage in a receptor-interacting protein 3 (RIP3)-dependent pathway, which was regulated by Toll-like receptor 4 (TLR4) dimerization. Further study illustrated that activated RIP3 evoked endoplasmic reticulum stress as well as reactive oxygen species generation. Both DHT and RIP3 silence reversed the above phenomena. In the in vivo experiment, aorta and serum samples were collected to determine features of plaque stability, including plaque size, necrotic core area, as well as collagen content in fibrous cap and the expression of related protein molecules. Both DHT and RIP3 inhibitor GSK872 significantly enhanced plaque stability in ApoE-/- mice by reducing oxidative stress, shrinking necrotic core area, increasing collagen content, and decreasing RIP3 expression. Innovation and Conclusion: Our study showed that DHT may stabilize vulnerable plaque by suppressing RIP3-mediated necroptosis of macrophage, which indicates its potential application as a lead compound for cardiovascular treatments, especially for advanced atherosclerosis. Antioxid. Redox Signal. 34, 351-363.
- Journal
- Antioxid Redox Signal
- Publish Year
- 2021
- Experiment Subject
- mouse; human
- Experiment Type
- Animal Experiment
- Phenotype Related
- Myocardial Infarction; Atherosclerosis; Acute Thrombus; Advanced Atherosclerosis
- Paper Title Cn
- Paper Title En
- Dihydrotanshinone I Attenuates Plaque Vulnerability in Apolipoprotein E-Deficient Mice: Role of Receptor-Interacting Protein 3
- Bilingual Status
- semi_complete