an-atherosclerosis-model-mice-induced-both-partial-carotid-ligation

An Atherosclerosis Model in Mice Induced by Both Partial Carotid Ligation and Overexpression of <em>PCSK9</em>

The lack of rapid, reproducible carotid-specific atherosclerosis models in wild-type mice limits translational studies of plaque biology and therapies. ...

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Body mass index (BMI) and blood biomarkers are not enough to predict cardiovascular disease risk. Apolipoprotein B was identified to be associated with cardiovascular disease (CVD) progression. The Dual-energy X-ray Absorption (DXA) results could be considered as a predictor for cardiovascular disease in a more refined way based on fat distribution. The prediction of CVD risk by simple indicators still cannot meet clinical needs. The association of ApoB with specific fat depot features remains to be explored to better co-predict cardiovascular disease risk. An amount of 5997 adults from National Health and Nutrition Examination Survey (NHANES) were enrolled. Their demographic information, baseline clinical condition, blood examination, and DXA physical examination data were collected. Multivariate regression was used to assess the correlation between ApoB and site-specific fat characteristics through different adjusted models. Smooth curve fittings and threshold analysis were used to discover the turning points with 95% confidence intervals. ApoB is positively correlated with arms percent fat, legs percent fat, trunk percent fat, android percent fat, gynoid percent fat, arm circumference and waist circumference after adjustment with covariates for age, gender, race, hypertension, diabetes, hyperlipidemia, coronary heart disease, smoking status and vigorous work activity. The smooth curve fitting and threshold analysis also showed that depot-specific fat had lower turning points of ApoB in both males and females within the normal reference range of ApoB. Meanwhile, females have a lower increase in ApoB per 1% total percent fat and android percent fat than males before the turning points, while females have a higher growth of ApoB per 1% gynoid percent fat than males. The combined specific fat-depot DXA and ApoB analysis could indicate the risk of CVD in advance of lipid biomarkers or DXA alone.

The Correlation of Apolipoprotein B with Alterations in Specific Fat Depots Content in Adults.

Macroautophagy/autophagy, is widely recognized for its crucial role in enabling cell survival and maintaining cellular energy homeostasis during starvation or energy stress. Its regulation is intricately linked to cellular energy status. In this review, covering yeast, mammals, and plants, we aim to provide a comprehensive overview of the understanding of the roles and mechanisms of carbon- or glucose-deprivation related autophagy, showing how cells effectively respond to such challenges for survival. Further investigation is needed to determine the specific degraded substrates by autophagy during glucose or energy deprivation and the diverse roles and mechanisms during varying durations of energy starvation. ADP: adenosine diphosphate; AMP: adenosine monophosphate; AMPK: AMP-activated protein kinase; ATG: autophagy related; ATP: adenosine triphosphate; ER: endoplasmic reticulum; ESCRT: endosomal sorting complex required for transport; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GD: glucose deprivation; GFP: green fluorescent protein; GTPases: guanosine triphosphatases; HK2: hexokinase 2; : ; LD: lipid droplet; MAP1LC3/LC3: microtubule-associated protein1 light chain 3; MAPK: mitogen-activated protein kinase; Mec1: mitosis entry checkpoint 1; MTOR: mechanistic target of rapamycin kinase; NAD (+): nicotinamide adenine dinucleotide; OGD: oxygen and glucose deprivation; PAS: phagophore assembly site; PCD: programmed cell death; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; ROS: reactive oxygen species; : ; SIRT1: sirtuin 1; Snf1: sucrose non-fermenting 1; STK11/LKB1: serine/threonine kinase 11; TFEB: transcription factor EB; TORC1: target of rapamycin complex 1; ULK1: unc-51 like kinase 1; Vps27: vacuolar protein sorting 27; Vps4: vacuolar protein sorting 4.

Interplay of energy metabolism and autophagy.

Uterine intravenous leiomyomatosis (IVL) is a rare and unique leiomyoma that is difficult to surgery due to its ability to extend into intra- and extra-uterine vasculature. And it is difficult to differentiate from uterine leiomyoma (LM) by conventional CT scanning, which results in a large number of missed diagnoses. This study aimed to evaluate the utility of a contrast-enhanced CT-based radiomic nomogram for preoperative differentiation of IVL and LM.

A contrast-enhanced CT-based radiomic nomogram for the differential diagnosis of intravenous leiomyomatosis and uterine leiomyoma.

Currently, noninvasive imaging techniques and circulating biomarkers are still insufficient to accurately assess carotid plaque stability, and an in-depth understanding of the molecular mechanisms that contribute to plaque instability is still lacking.

Characterization of the proteome of stable and unstable carotid atherosclerotic plaques using data-independent acquisition mass spectrometry.

The autophagy initiation complex is brought about via a highly ordered and stepwise assembly process. Two crucial signaling molecules, mTORC1 and AMPK, orchestrate this assembly by phosphorylating/dephosphorylating autophagy-related proteins. Activation of Atg1 followed by recruitment of both Atg9 vesicles and the PI3K complex I to the PAS (phagophore assembly site) are particularly crucial steps in its formation. Ypt1, a small Rab GTPase in yeast cells, also plays an essential role in the formation of the autophagy initiation complex through multiple regulatory pathways. In this review, our primary focus is to discuss how signaling molecules initiate the assembly of the autophagy initiation complex, and highlight the significant roles of Ypt1 in this process. We end by addressing issues that need future clarification.

The molecular mechanisms regulating the assembly of the autophagy initiation complex.

The incidence of splenic artery aneurysms (SAAs) has increased with advances in imaging techniques, necessitating a comprehensive classification to guide treatment strategies. This study aims to propose a novel classification system for SAAs based on aneurysm characteristics and to review treatment outcomes at our center.

Treatment strategy for splenic artery aneurysms and novel classification based on imaging.

ObjectivesCarotid artery dissection (CAD) is a significant cause of strokes in young individuals, leading to severe complications and socioeconomic burdens. Despite antithrombotic therapy being the primary management strategy, optimal treatment for patients with recurrent or worsening symptoms remains undefined. This study aims to describe the characteristics and evaluate the outcomes of conservative versus surgical management in CAD patients.MethodsA total of 23 patients presenting with CAD from November 2014 to December 2021 were reviewed retrospectively. Patient demographics, vascular risk factors, symptoms, imaging results, treatment details, and follow-up information were collected and analyzed. Propensity score matching (PSM) was utilized to enhance comparability.ResultsThe mean age of the patients was 46.4 ± 9.4 years, with a median follow-up of 12 (range 3-90) months. Of the 23 patients reviewed, seven underwent endovascular treatment or open surgery due to unresponsiveness to conservative therapy, while 16 received conservative management. All patients showed regression of symptoms. Surgical patients showed a significant improvement with a 100% patency rate during the follow-up. PS matching adjusted for baseline differences, yielding comparable groups for analysis. No significant difference between treatment approaches was observed in stroke recurrence rates, although surgical intervention showed promising outcomes in symptom resolution and stroke prevention.ConclusionBoth conservative and surgical management of CAD can lead to favorable outcomes. While conservative therapy remains the initial approach and proves effective, surgery appears beneficial and safe in certain cases unresponsive to conservative treatment. Further investigation through larger prospective and randomized trials is necessary to establish its safety and efficacy.

Comparative outcomes of surgical and conservative management in carotid artery dissection.

Aortic aneurysm and dissection (AAD) are vascular disorders with high mortality. Previous evidence has suggested an elevated risk of AAD associated with the use of phosphodiesterase 5A (PDE5A) inhibitors. PDE5A, a cGMP-hydrolyzing enzyme, is enriched in vascular smooth muscle cells (SMCs), but the role of SMC-specific PDE5A in the pathogenesis of AAD is still unclear. In this study, PDE5A expression in human and mouse aortic tissues was analyzed by single-cell RNA sequencing (scRNA-seq), western blotting, immunofluorescence, and immunohistochemistry staining. SMC-specific PDE5A knockout (PDE5A) and PDE5A-overexpressing (PDE5A) mice were constructed and utilized, along with an AAD mouse model induced by a high-fat diet and angiotensin II (Ang II) infusion. In vivo imaging and histological analyses were performed to assess aortic pathologies. PDE5A expression was reduced in human and mouse AAD aortic tissues, primarily in SMCs. Pharmacological inhibition or genetic knockout of PDE5A in SMCs exacerbated aortic wall dilatation and elastin fiber degradation, increasing AAD incidence. In contrast, the AAD phenotype was rescued in challenged PDE5A mice. Mechanistically, PDE5A expression influenced myosin light chain (MLC) phosphorylation, a key regulator of SMC contractility. In AAD tissues from PDE5A mice, increased cGMP-dependent protein kinase (PKG) activation and decreased MLC phosphorylation indicate enhanced aortic relaxation. In conclusion, our findings suggest that PDE5A downregulation or inhibition plays a causative role in exacerbating AAD likely by potentiating cGMP/PKG-mediated aortic SMC relaxation. Our findings highlight the need for caution in the clinical use of PDE5 inhibitors in patients at risk of aortic diseases. © 2025 The Pathological Society of Great Britain and Ireland.

Phosphodiesterase 5 inactivation in vascular smooth muscle cells aggravates aortic aneurysm and dissection.

Tertiary lymphoid organs have been identified in the arterial adventitia in both mouse models of atherosclerosis and patients with atherosclerosis, yet their role in the disease remains insufficiently explored. Here we present a spatially resolved single-cell transcriptome atlas of human atherosclerotic plaques, identifying 14 distinct cell types and providing evidence of plaque tertiary lymphoid organs (PTLOs). The development of PTLOs was associated with the expression of lymphangiogenic chemokine genes and the adhesion molecule gene in fibroblast-like smooth muscle cells. PTLOs harbor abundant B cells with expanded and diversified B cell receptors, suggesting substantial immune involvement. We also observed that B cells may be exchanged between PTLOs and perivascular adipose tissues. The presence of PTLO-like structures correlates with cerebrovascular events, which may be mediated by PTLO-derived IgG antibodies enhancing macrophage functional activity. Our findings suggest the existence and characteristics of PTLOs in human atherosclerosis, elucidating their cellular functions and clinical implications and offering avenues for understanding, diagnosing and treating this condition.

Single-cell spatial transcriptomics of tertiary lymphoid organ-like structures in human atherosclerotic plaques.

Atherosclerosis is a major contributor to cardiovascular diseases worldwide. Despite advancements in understanding its pathology, significant gaps remain in the molecular characterization of atherosclerotic plaques. This study addresses this gap by extensively profiling the proteomic landscape of carotid atherosclerotic plaques, classified under the American Heart Association (AHA) types IV to VI, to identify potential biomarkers and therapeutic targets.

Molecular landscape of atherosclerotic plaque progression: insights from proteomics, single-cell transcriptomics and genomics.

Atherosclerosis in the carotid artery significantly contributes to embolic events leading to ischemic stroke. Precise identification of unstable carotid plaques through non-invasive imaging, is pivotal for stroke prevention. Artificial intelligence (AI) has demonstrated promise in enhancing the accuracy of plaque risk stratification. This review aims to assess the diagnostic performance of AI algorithms in distinguishing unstable carotid plaques from stable plaques using medical imaging.

Artificial intelligence diagnostic performance in image-based vulnerable carotid plaque detection: a systematic review and meta-analysis.

This study aims to develop a radiomics model based on carotid perivascular adipose tissue (PVAT) from CT angiography to identify histologically confirmed vulnerable plaques in patients with carotid artery stenosis (CAS).

Article	Year
The Correlation of Apolipoprotein B with Alterations in Specific Fat Depots Content in Adults. International journal of molecular sciences\| PubMed ID: 37047284	2023
Interplay of energy metabolism and autophagy. Autophagy\| PubMed ID: 37594406	2024
A contrast-enhanced CT-based radiomic nomogram for the differential diagnosis of intravenous leiomyomatosis and uterine leiomyoma. Frontiers in oncology\| PubMed ID: 37681025	2023
Characterization of the proteome of stable and unstable carotid atherosclerotic plaques using data-independent acquisition mass spectrometry. Journal of translational medicine\| PubMed ID: 38454421	2024
The molecular mechanisms regulating the assembly of the autophagy initiation complex. BioEssays : news and reviews in molecular, cellular and developmental biology\| PubMed ID: 38593284	2024
Treatment strategy for splenic artery aneurysms and novel classification based on imaging. Journal of vascular surgery\| PubMed ID: 38768832	2024
Comparative outcomes of surgical and conservative management in carotid artery dissection. Vascular\| PubMed ID: 39368078	2025
Phosphodiesterase 5 inactivation in vascular smooth muscle cells aggravates aortic aneurysm and dissection. The Journal of pathology\| PubMed ID: 40145405	2025
Single-cell spatial transcriptomics of tertiary lymphoid organ-like structures in human atherosclerotic plaques. Nature cardiovascular research\| PubMed ID: 40295810	2025
Molecular landscape of atherosclerotic plaque progression: insights from proteomics, single-cell transcriptomics and genomics. BMC medicine\| PubMed ID: 40307879	2025
Artificial intelligence diagnostic performance in image-based vulnerable carotid plaque detection: a systematic review and meta-analysis. BMC medical informatics and decision making\| PubMed ID: 41219882	2025
Identification of histological carotid plaque vulnerability by CT angiography using perivascular adipose tissue radiomics signature. Insights into imaging\| PubMed ID: 41491918	2026

Yuyao Feng

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