Evidence mapPaperPMID 39633391Full record

ArticleCardiovascular diabetology2024

PACS2/CPT1A/DHODH signaling promotes cardiomyocyte ferroptosis in diabetic cardiomyopathy.

Hong Xiang, Qi Lyu, Shuhua Chen, Jie Ouyang, Di Xiao, Quanjun Liu, HaiJiao Long, Xinru Zheng, Xiaoping Yang, Hongwei Lu

Abstract read
In one paragraph

Article in Cardiovascular diabetology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Hong XiangKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China.
Qi LyuKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China.
Shuhua ChenDepartment of Biochemistry, School of Life Sciences of Central South University, Changsha, Hunan, China.
Jie OuyangDepartment of Cardiology, Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Di XiaoKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China.
Quanjun LiuDepartment of Cardiology, Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
HaiJiao LongDepartment of Cardiology, Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Xinru ZhengDepartment of Cardiology, Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Xiaoping YangKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China. Xiaoping.Yang@hunnu.edu.cn.
Hongwei LuCenter for Experimental Medicine, The Third Xiangya Hospital of Central South University, Changsha, China. hongweilu@csu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesThe pathophysiology of diabetic cardiomyopathy (DCM) is a phenomenon of great interest, but its clinical problems have not yet been effectively addressed. Recently, the mechanism of ferroptosis in the pathophysiology of various diseases, including DCM, has attracted widespread attention. Here, we explored the role of PACS2 in ferroptosis in DCM through its downregulation of PACS2 expression. METHODS AND

resultsCardiomyocytes were treated with high glucose and palmitic acid (HGPA), and the detection of cardiomyocyte iron ions, lipid peroxides, and reactive oxygen species (ROS) revealed clear ferroptosis during these treatments. Silencing PACS2 downregulated CPT1A expression and upregulated DHODH expression significantly, reversing HGPA-induced ferroptosis. Further silencing of PACS2 with a CPT1A agonist exacerbated cardiomyocyte ferroptosis while promoting mitochondrial damage in cardiomyocytes. Using a mouse model of type 2 diabetes induced by streptozotocin (STZ) and a high-fat diet (HFD), we found that PACS2 deletion reversed these treatment-induced increases in cellular iron ions, impaired cardiac function, mitochondrial damage and ferroptosis in cardiac muscle tissues.

conclusionsThe PACS2/CPT1A/DHODH signalling pathway may be involved in ferroptosis in DCM by regulating cardiomyocyte mitochondrial function.

Indexed as

Carnitine O-PalmitoyltransferaseDiabetes Mellitus, ExperimentalDiabetic CardiomyopathiesFerroptosisMice, Inbred C57BLMice, KnockoutMyocytes, CardiacSignal TransductionAnimalsDiabetes Mellitus, Type 2Diet, High-FatMaleMiceMitochondria, HeartPalmitic AcidReactive Oxygen SpeciesCarnitine O-PalmitoyltransferaseCPT1B protein, mousePalmitic AcidReactive Oxygen SpeciesDiabetic cardiomyopathyFerroptosisMitochondria

Identifiers

PMID39633391
PMCPMC11619700

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.