Background: The primary cause of acute cardiovascular events with high mortality is the rupture of atherosclerotic plaque followed by thrombosis. Sodium Danshensu (SDSS) has shown potential in inhibiting the inflammatory response in macrophages and preventing early plaque formation in atherosclerotic mice. However, the specific targets and detailed mechanism of action of SDSS are still unclear.
Objective: This study aims to investigate the efficacy and mechanism of SDSS in inhibiting inflammation in macrophages and stabilizing vulnerable plaques in atherosclerosis (AS).
Materials And Methods: The efficacy of SDSS in stabilizing vulnerable plaques was demonstrated using various techniques such as ultrasound, Oil Red O staining, HE staining, Masson staining, immunohistochemistry, and lipid analysis in ApoE mice. Subsequently, IKKβ was identified as a potential target of SDSS through protein microarray, network pharmacology analysis, and molecular docking. Additionally, ELISA, RT-qPCR, Western blotting, and immunofluorescence were employed to measure the levels of inflammatory cytokines, IKKβ, and NF-κB pathway-related targets, thereby confirming the mechanism of SDSS in treating AS both in vivo and in vitro. Finally, the impact of SDSS was observed in the presence of an IKKβ-specific inhibitor.
Results: Initially, the administration of SDSS led to a decrease in the formation and area of aortic plaque, while also stabilizing vulnerable plaques in ApoE mice. Furthermore, it was identified that IKKβ serves as the primary binding target of SDSS. Additionally, both in vivo and in vitro experiments demonstrated that SDSS effectively inhibits the NF-κB pathway by targeting IKKβ. Lastly, the combined use of the IKKβ-specific inhibitor IMD-0354 further enhanced the beneficial effects of SDSS.
Conclusions: SDSS stabilized vulnerable plaques and suppressed inflammatory responses by inhibiting the NF-κB pathway through its targeting of IKKβ.
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http://dx.doi.org/10.1016/j.biopha.2023.115153 | DOI Listing |
J Am Heart Assoc
January 2025
Research Institute of Internal Medicine, Oslo University Hospital Oslo Norway.
Background: Complement activation may promote atherosclerosis. Yet, data on the to which extent complement, and more specifically the alternative complement pathway, is activated in patients with carotid atherosclerosis and related to adverse outcome in these patients, are scarce.
Methods And Results: We measured, by ELISA, plasma levels of factor D, properdin, C3bBbP (C3 convertase), and factor H in patients with advanced carotid atherosclerosis in a (n=324) and in a (n=206) cohort in relation to adverse outcome (mean follow-up 7.
J Atheroscler Thromb
January 2025
Department of Neurology, National Cerebral and Cardiovascular Center.
Aim: Branch atheromatous disease (BAD), characterized by the occlusion of perforating branches near the orifice of a parent artery, often develops early neurological deterioration because the mechanisms underlying BAD remain unclear. Abnormal wall shear stress (WSS) is strongly associated with endothelial dysfunction and plaque growth or rupture. Therefore, we hypothesized that computational fluid dynamics (CFD) modeling could detect differences in WSS between BAD and small-vessel occlusion (SVO), both of which result from perforating artery occlusion/stenosis.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2025
Department of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41500 Larissa, Greece.
Background: Hypoxia-inducible factor 1 alpha (HIF-1α) and its related vascular endothelial growth factor (VEGF) may play a significant role in atherosclerosis and their targeting is a strategic approach that may affect multiple pathways influencing disease progression. This study aimed to perform a systematic review to reveal current evidence on the role of HIF-1α and VEGF immunophenotypes with other prognostic markers as potential biomarkers of atherosclerosis prognosis and treatment efficacy.
Methods: We performed a systematic review of the current literature to explore the role of HIF-1α and VEGF protein expression along with the relation to the prognosis and therapeutic strategies of atherosclerosis.
J Clin Med
January 2025
Operative Unit of Vascular Surgery, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy.
: Carotid artery stenosis (CAS) is one of the main causes of stroke, and the vulnerability of plaque has been proved to be a determinant. A joint analysis of shear wave elastography, a radiofrequency echo-based wall tracking technique for arterial stiffness evaluation, and of autonomic and baroreflex function is proposed to noninvasively, preoperatively assess plaque vulnerability in asymptomatic CAS patients scheduled for carotid endarterectomy. : Elastographic markers of arterial stiffness were derived preoperatively in 78 CAS patients (age: 74.
View Article and Find Full Text PDFAnn Vasc Surg
January 2025
Division of Vascular and Endovascular Surgery, Mayo Clinic, Jacksonville, FL. Electronic address:
Introduction: Carotid artery stenosis is a significant contributor to ischemic strokes, and its surgical management includes carotid artery endarterectomy (CEA), transfemoral carotid artery stenting (TF-CAS), and trans carotid artery revascularization (TCAR). CEA has traditionally been preferred, but TF-CAS and TCAR are also excellent alternative options if the anatomy of the vessels allows them. This study reports our short- and mid-term outcomes after carotid artery revascularization in symptomatic patients at a stroke center.
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