NOTCH3 as a modulator of vascular disease: a target in elastin deficiency and arterial pathologies

Malka, Kimberly T.; Liaw, Lucy

doi:10.1172/jci157007

Cited by 4 publications

(1 citation statement)

References 23 publications

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“…Consistently, GLUT1 suppression significantly reduced melanoma cell proliferation, apoptosis resistance and migratory activity, unraveling the favorable role of GLUT1 in melanoma cell metastatic behavior 35 . NOTCH3 belongs to the classic Notch family and acts as signaling receptors to dominate cell fate in many tissue contexts 36 . NOTCH3 mediates the communication between melanoma cells and endothelial cells, thus promoting tumor cell migration 37 .…”

Section: Discussionmentioning

confidence: 99%

A comprehensive signature based on endoplasmic reticulum stress-related genes in predicting prognosis and immunotherapy response in melanoma

Liu,

Yao,

Chen

et al. 2023

Sci Rep

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Melanoma is considered as one of the most invasion types of skin cancer with high mortality rates. Although combination of immune checkpoint therapy with local surgical excision provide a novel promising therapeutic strategies, the overall prognosis of melanoma patients remains unsatisfactory. Endoplasmic reticulum (ER) stress, a process of protein misfolding and undue accumulation, has been proven to play an indispensable regulatory role in tumor progression and tumor immunity. However, whether the signature based ER genes has predictive value for the prognosis and immunotherapy of melanoma has not been systematically manifested. In this study, the LASSO regression and multivariate Cox regression were applied to construct a novel signature for predicting melanoma prognosis both in the training and testing set. Intriguingly, we found that patients endowed with high- and low-risk scores displayed differences in clinicopathologic classification, immune cell infiltration level, tumor microenvironment, and immune checkpoint treatment response. Subsequently, based on molecular biology experiments, we validated that silencing the expression of RAC1, an ERG composed of the risk signature, could restrain the proliferation and migration, promote apoptosis, as well as increase the expression of PD-1/PD-L1 and CTLA4 in melanoma cells. Taken together, the risk signature was regarded as promising predictors for melanoma prognosis and might provide prospective strategies to ameliorate patients’ response to immunotherapy.

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Section: Discussionmentioning

confidence: 99%

A comprehensive signature based on endoplasmic reticulum stress-related genes in predicting prognosis and immunotherapy response in melanoma

Liu,

Yao,

Chen

et al. 2023

Sci Rep

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Risk of major vascular events in patients without traditional risk factors after transient ischemic attack or minor ischemic stroke: An international prospective cohort

Uchiyama,

Hoshino,

Minematsu

et al. 2024

European Stroke Journal

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Introduction: To investigate the clinical characteristics in patients without traditional risk factors (TRFs) after transient ischemic attack or minor ischemic stroke, who were recruited in the TIAregistry.org. Patients and methods: A total of 3847 patients were analyzed. TRFs included hypertension, diabetes, hypercholesterolemia, current smoking, and atrial fibrillation. Background characteristics and outcomes at 1 and 5 years in patients without TRFs were compared to those in patients with TRFs. The primary outcome was major cardiovascular event (MACE), which was non-fatal stroke, non-fatal acute coronary syndrome, or vascular death. To evaluate the causes, we applied the ASCOD (atherosclerosis, small vessel disease, cardiac pathology, other causes or dissection) grading system. Results: One-year risk of MACE (5.3% vs 6.3%, hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.53–1.31) was comparable between patients without TRFs ( n = 402) and those with TRFs ( n = 3445). Five-year risk of MACE was significantly lower in patients without TRFs than in those with TRFs (7.9% vs 13.9%, HR 0.57, 95% CI 0.39–0.82). In patients without TRFs, causal atherosclerosis was a potent risk factor (HR 5.67, 95% CI 2.68–12.02) and ipsilateral extra- or intra-cranial arterial stenosis was only significant predictor of MACE (interaction p = 0.0046) at 5 years. Conclusion and discussion: The 5-year risk of MACE was lower in patients without TRFs than those with TRFs, although a certain level of risk persisted in the absence of TRFs. The most significant predictor of MACE in patients without TRFs was arterial stenosis.

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Cardiovascular Disease May Be Triggered by Gut Microbiota, Microbial Metabolites, Gut Wall Reactions, and Inflammation

Dicks

2024

IJMS

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Cardiovascular disease (CVD) may be inherited, as recently shown with the identification of single nucleotide polymorphisms (SNPs or “snips”) on a 250 kb DNA fragment that encodes 92 proteins associated with CVD. CVD is also triggered by microbial dysbiosis, microbial metabolites, metabolic disorders, and inflammatory intestinal epithelial cells (IECs). The epithelial cellular adhesion molecule (Ep-CAM) and trefoil factor 3 (TFF3) peptide keeps the gut wall intact and healthy. Variations in Ep-CAM levels are directly linked to changes in the gut microbiome. Leptin, plasminogen activator inhibitor 1 (PAI1), and alpha-1 acid glycoprotein 1 (AGP1) are associated with obesity and may be used as biomarkers. Although contactin 1 (CNTN1) is also associated with obesity and adiposity, it regulates the bacterial metabolism of tryptophan (Trp) and thus appetite. A decrease in CNTN1 may serve as an early warning of CVD. Short-chain fatty acids (SCFAs) produced by gut microbiota inhibit pro-inflammatory cytokines and damage vascular integrity. Trimethylamine N-oxide (TMAO), produced by gut microbiota, activates inflammatory Nod-like receptors (NLRs) such as Nod-like receptor protein 3 (NLRP3), which increase platelet formation. Mutations in the elastin gene (ELN) cause supra valvular aortic stenosis (SVAS), defined as the thickening of the arterial wall. Many of the genes expressed by human cells are regulated by gut microbiota. The identification of new molecular markers is crucial for the prevention of CVD and the development of new therapeutic strategies. This review summarizes the causes of CVD and identifies possible CVD markers.

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NOTCH3 as a modulator of vascular disease: a target in elastin deficiency and arterial pathologies

Cited by 4 publications

References 23 publications

A comprehensive signature based on endoplasmic reticulum stress-related genes in predicting prognosis and immunotherapy response in melanoma

A comprehensive signature based on endoplasmic reticulum stress-related genes in predicting prognosis and immunotherapy response in melanoma

Risk of major vascular events in patients without traditional risk factors after transient ischemic attack or minor ischemic stroke: An international prospective cohort

Cardiovascular Disease May Be Triggered by Gut Microbiota, Microbial Metabolites, Gut Wall Reactions, and Inflammation

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