Publications by authors named "Dingsheng Jiang"

Advanced atherosclerosis is the pathological basis for acute cardiovascular events, with significant residual risk of recurrent clinical events despite contemporary treatment. The death of foamy macrophages is a main contributor to plaque progression, but the underlying mechanisms remain unclear. Bulk and single-cell RNA sequencing demonstrated that massive iron accumulation in advanced atherosclerosis promoted foamy macrophage ferroptosis, particularly in low expression of triggering receptor expressed on myeloid cells 2 (TREM2) foamy macrophages.

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  • * A study identified glycolysis-related pathways, particularly focusing on lactate dehydrogenase A (LDHA), which was found to promote VSMC ferroptosis and lipid peroxidation when overexpressed.
  • * There is a negative correlation between elevated LDHA and protective ferroptosis-related molecules, and the interaction with the NRF2 protein suggests that targeting LDHA could be a potential strategy for preventing or treating AD.
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  • Klf9, a protein linked to heart health, is found to be dysregulated in heart disease, leading to issues like hypertrophic cardiomyopathy in mice.
  • Deleting Klf9 results in poorly functioning mitochondria and reduced mitophagy, which worsens heart failure when exposed to angiotensin II.
  • Enhancing Klf9 activity or rescuing related proteins can improve heart function, suggesting that targeting Klf9 may be a promising treatment for heart failure.
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During oxidative phosphorylation, mitochondria continuously produce reactive oxygen species (ROS), and untimely ROS clearance can subject mitochondria to oxidative stress, ultimately resulting in mitochondrial damage. Mitophagy is essential for maintaining cellular mitochondrial quality control and homeostasis, with activation involving both ubiquitin-dependent and ubiquitin-independent pathways. Over the past decade, numerous studies have indicated that different forms of regulated cell death (RCD) are connected with mitophagy.

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PANoptosis is a unique innate immune inflammatory lytic cell death pathway initiated by an innate immune sensor and driven by caspases and RIPKs. As a distinct pathway, the execution of PANoptosis cannot be hindered by targeting other cell death pathways, such as pyroptosis, apoptosis, or necroptosis. Instead, targeting key PANoptosome components can serve as a strategy to prevent this form of cell death.

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  • Abnormal growth of pulmonary artery smooth muscle cells (PASMCs) contributes to pulmonary hypertension (PH), leading researchers to explore new treatment options.
  • This study found an increased expression of metallothionein 3 (MT3) in human patients and animal models of PH, linking it to cell proliferation and autophagy.
  • The research suggests a new pathway involving MT3, zinc, MTF1, and ATG5 that regulates PASMC growth and autophagosome formation, highlighting MT3 as a potential therapeutic target for PH.
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Myocardial infarction (MI) is a life-threatening cardiovascular disease that, on average, results in 8.5 million deaths worldwide each year. Timely revascularization of occluded vessels is a critical method of myocardial salvage.

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Background: Hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs) and consequent pulmonary vascular remodeling are the crucial pathological features of pulmonary hypertension (PH). Protein methylation has been shown to be critically involved in PASMC proliferation and PH, but the underlying mechanism remains largely unknown.

Methods: PH animal models were generated by treating mice/rats with chronic hypoxia for 4 weeks.

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Previous studies have shown that ferroptosis of vascular smooth muscle cells (VSMCs) is involved in the development of aortic dissection (AD) and that histone methylation regulates this process. SP2509 acts as a specific inhibitor of lysine-specific demethylase 1 (LSD1), which governs a variety of biological processes. However, the effect of SP2509 on VSMC ferroptosis and AD remains to be elucidated.

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  • Coronary restenosis significantly affects long-term outcomes for patients with coronary heart disease, highlighting its clinical importance.
  • Elevated expression of lysine methyltransferase SMYD2 in vascular smooth muscle cells and injured carotid artery tissues promotes neointimal hyperplasia, while its inhibition or knockdown reduces VSMC phenotypic switching and neointima formation.
  • The study identifies a novel mechanism involving the SMYD2-HDAC3-SRF axis, where SMYD2 enhances HDAC3 activity, influencing VSMC proliferation and potentially offering new therapeutic targets for managing coronary restenosis.
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Histone methyltransferase SETDB1 (SET domain bifurcated histone lysine methyltransferase 1, also known as ESET or KMT1E) is known to be involved in the deposition of the di- and tri-methyl marks on H3K9 (H3K9me2 and H3K9me3), which are associated with transcription repression. SETDB1 exerts an essential role in the silencing of endogenous retroviruses (ERVs) in embryonic stem cells (mESCs) by tri-methylating H3K9 (H3K9me3) and interacting with DNA methyltransferases (DNMTs). Additionally, SETDB1 is engaged in regulating multiple biological processes and diseases, such as ageing, tumors, and inflammatory bowel disease (IBD), by methylating both histones and non-histone proteins.

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Myocardial ischemia-reperfusion (I/R) injury most commonly occurs in coronary artery disease when prompt reperfusion is used to salvage the ischemic myocardium. Cardiomyocyte death is a significant component of myocardial I/R injury and its mechanism was previously thought to be limited to apoptosis and necrosis. With the discovery of novel types of cell death, ferroptosis, necroptosis, and pyroptosis have been shown to be involved in myocardial I/R.

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Background: Aberrant proliferation of vascular smooth muscle cells (VSMCs) is the cause of neointima formation followed by vascular injury. Autophagy is involved in this pathological process, but its function is controversial. Recently, we found that methyltransferase like 3 (METTL3) inhibited VSMC proliferation by activating autophagosome formation.

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Ferroptosis is a form of programmed cell death characterized by elevated intracellular ferrous ion levels and increased lipid peroxidation. Since its discovery and characterization in 2012, considerable progress has been made in understanding the regulatory mechanisms and pathophysiological functions of ferroptosis. Recent findings suggest that numerous organ injuries ( ischemia/reperfusion injury) and degenerative pathologies ( aortic dissection and neurodegenerative disease) are driven by ferroptosis.

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Background: E1A-associated 300-kDa protein (P300), an endogenous histone acetyltransferase, contributes to modifications of the chromatin landscape of genes involved in multiple cardiovascular diseases. Ferroptosis of vascular smooth muscle cells (VSMCs) is a novel pathological mechanism of aortic dissection. However, whether P300 regulates VSMC ferroptosis remains unknown.

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The behavior of vascular smooth muscle cells (VSMCs) contributes to the formation of neointima. We previously found that EHMT2 suppressed autophagy activation in VSMCs. BRD4770, an inhibitor of EHMT2/G9a, plays a critical role in several kinds of cancers.

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Ferroptosis is a form of regulated cell death triggered by the iron-dependent peroxidation of phospholipids. Interactions of iron and lipid metabolism factors jointly promote ferroptosis. Ferroptosis has been demonstrated to be involved in the development of various diseases, such as tumors and degenerative diseases (e.

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Ferroptosis is an iron-dependent regulated cell death driven by excessive lipid peroxidation. Inflammation is one common and effective physiological event that protects against various stimuli to maintain tissue homeostasis. However, the dysregulation of inflammatory responses can cause imbalance of the immune system, cell dysfunction and death.

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Prevention of neointima formation is the key to improving long-term outcomes after stenting or coronary artery bypass grafting. RNA N -methyladenosine (m A) methylation has been reported to be involved in the development of various cardiovascular diseases, but whether it has a regulatory effect on neointima formation is unknown. Herein, we revealed that methyltransferase-like 3 (METTL3), the major methyltransferase of m A methylation, was downregulated during vascular smooth muscle cell (VSMC) proliferation and neointima formation.

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Autophagy is a well-conserved biological process that maintains homeostasis. Accumulating evidence has revealed that autophagy plays an important role in various cardiovascular diseases, such as aneurysm, aortic dissection, atherosclerosis, and myocardial ischemia-reperfusion injury. Here, we summarize the current experimental evidence on the function of autophagy and autophagy proteins in aortic aneurysm and dissection (AAD).

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Background: Vascular smooth muscle cell (VSMC) phenotype switching is critical for neointima formation, which is the major cause of restenosis after stenting or coronary artery bypass grafting. However, the epigenetic mechanisms regulating phenotype switching of VSMCs, especially histone methylation, are not well understood. As a main component of histone lysine demethylases, Jumonji demethylases might be involved in VSMC phenotype switching and neointima formation.

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Background: The misdiagnosis of aortic dissection (AD) can lead to a catastrophic prognosis. There is currently a lack of stable serological indicators with excellent efficacy for the differential diagnosis of AD and coronary artery disease (CAD). A recent study has shown an association between AD and iron metabolism.

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A variety of programmed cell death types have been shown to participate in the loss of smooth muscle cells (SMCs) during the development of aortic dissection (AD), but it is still largely unclear whether ferroptosis is involved in the development of AD. In the present study, we found that the expression of key ferroptosis regulatory proteins, solute carrier family 7 member 11 (SLC7A11), ferroptosis suppressor protein 1 (FSP1) and glutathione peroxidase 4 (GPX4) were downregulated in aortas of Stanford type A AD (TAAD) patients, and liproxstatin-1, a specific inhibitor of ferroptosis, obviously abolished the β-aminopropionitrile (BAPN)-induced development and rupture of AD in mice. Furthermore, the expression of methyltransferase-like 3 (METTL3), a major methyltransferase of RNA mA, was remarkably upregulated in the aortas of TAAD patients, and the protein levels of METTL3 were negatively correlated with SLC7A11 and FSP1 levels in human aortas.

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