Focus on Atherosclerosis and Lipids

Halász, Géza; Piepoli, Massimo F

doi:10.1093/eurjpc/zwab090

Cited by 5 publications

(4 citation statements)

References 26 publications

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“…Ox-LDL concentration is a critical marker for AS risk and a primary therapeutic target for AS [28]. Macrophages avidly internalize Ox-LDL, accumulating lipids to form "foam cells", contributing to lipid droplet accumulation.…”

Section: Anti-lipid Oxidation and Lipid Efflux Promotion In Vitromentioning

confidence: 99%

Foam Cell Targeted Liposomes Co-Encapsulating Superoxide Dismutase and Catalase to Attenuate Atherosclerosis by Inhibiting Oxidative Stress

Zhang,

Liu,

Zhang

et al. 2024

Discovery Medicine

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Background: Oxidative stress, propelled by reactive oxygen species (ROS), serves as a significant catalyst for atherosclerosis (AS), a primary contributor to vascular diseases on a global scale. Antioxidant therapy via nanomedicine has emerged as a pivotal approach in AS treatment. Nonetheless, challenges such as inadequate targeting, subpar biocompatibility, and limited antioxidant effectiveness have restrained the widespread utilization of nanomedicines in AS treatment. This study aimed to synthesize a specialized peptide-modified liposome capable of encapsulating two antioxidant enzymes, intending to enhance targeted antioxidant therapy for AS. Methods: The film dispersion method was employed for liposome preparation. Fluorescence quantification was conducted to assess the drug encapsulation rate. Characterization of liposome particle size was performed using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Laser confocal microscopy and flow cytometry were utilized to analyze liposome cell uptake and target foam cells. Antioxidant analysis was conducted using 2 ′ ,7 ′ -Dichlorodihydrofluorescein diacetate (DCFH-DA) staining, while pro-lipid efflux analysis utilized Oil Red O (ORO) staining. Safety evaluation was performed using Hematoxylin and Eosin (H&E) staining. The level of inflammatory factors was determined through enzyme-linked immunosorbent assay (ELISA). The degree of lipid oxidation at the cellular level was assessed using the malonaldehyde (MDA) assay. In vivo targeting analysis was conducted using small animal live imaging. Results: Our in vitro and in vivo findings substantiated that the modification of Lyp-1 led to increased delivery of antioxidant enzymes into foam cells (p < 0.05), the primary pathological cells within AS plaques. Upon accumulation in foam cells, liposomes loaded with superoxide dismutase (SOD) and catalase (CAT) (LyP-lip@SOD/CAT) effectively mitigated excess ROS and shielded macrophages from ROS-induced damage (p < 0.01). Furthermore, the reduction in ROS levels notably hindered the endocytosis of oxidized low-density lipoprotein (Ox-LDL) by activated macrophages, subsequently alleviating lipid accumulation at atherosclerotic lesion sites, evident from both in vitro and in vivo ORO staining results (p < 0.01). LyP-lip@SOD/CAT significantly curbed the secretion of inflammatory factors at the plaque site (p < 0.001). Additionally, LyP-lip@SOD/CAT demonstrated commendable biological safety. Conclusions: In this study, we effectively synthesized LyP-lip@SOD/CAT and established its efficacy as a straightforward and promising nano-agent for antioxidant therapy targeting atherosclerosis.

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Section: Anti-lipid Oxidation and Lipid Efflux Promotion In Vitromentioning

confidence: 99%

Foam Cell Targeted Liposomes Co-Encapsulating Superoxide Dismutase and Catalase to Attenuate Atherosclerosis by Inhibiting Oxidative Stress

Zhang,

Liu,

Zhang

et al. 2024

Discovery Medicine

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“…During AS development, lipid accumulation within the arterial intima attracts numerous inflammatory cells to the vascular endothelium, resulting in the prolonged production of cytokines and reactive oxygen species (ROS). These ROS further oxidize low‐density lipoproteins (LDL) into oxidized LDL (ox‐LDL), facilitating foam cell formation (Halasz & Piepoli, 2021). A study by Yang et al (2018) revealed that tanshinone C activates peroxidase 1 transcription via the Nrf2/ARE pathway, leading to enhanced peroxidase 1 expression in macrophages.…”

Section: Nrf2/are Signaling Pathwaymentioning

confidence: 99%

Modulation of atherosclerosis‐related signaling pathways by Chinese herbal extracts: Recent evidence and perspectives

Liu,

Guo,

Zhang

2024

Phytotherapy Research

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Atherosclerotic cardiovascular disease remains a preeminent cause of morbidity and mortality globally. The onset of atherosclerosis underpins the emergence of ischemic cardiovascular diseases, including coronary heart disease (CHD). Its pathogenesis entails multiple factors such as inflammation, oxidative stress, apoptosis, vascular endothelial damage, foam cell formation, and platelet activation. Furthermore, it triggers the activation of diverse signaling pathways including Phosphatidylinositol 3‐kinase/protein kinase B (PI3K/Akt), NF‐E2‐related factor 2/antioxidant response element (Nrf2/ARE), the Notch signaling pathway, peroxisome proliferator‐activated receptor (PPAR), nucleotide oligo‐structural domain‐like receptor thermoprotein structural domain‐associated protein 3 (NLRP3), silencing information regulator 2‐associated enzyme 1 (Sirt1), nuclear transcription factor‐κB (NF‐κB), Circular RNA (Circ RNA), MicroRNA (mi RNA), Transforming growth factor‐β (TGF‐β), and Janus kinase‐signal transducer and activator of transcription (JAK/STAT). Over recent decades, therapeutic approaches for atherosclerosis have been dominated by the utilization of high‐intensity statins to reduce lipid levels, despite significant adverse effects. Consequently, there is a growing interest in the development of safer and more efficacious drugs and therapeutic modalities. Traditional Chinese medicine (TCM) offers a vital strategy for the prevention and treatment of cardiovascular diseases. Numerous studies have detailed the mechanisms through which TCM active ingredients modulate signaling molecules and influence the atherosclerotic process. This article reviews the signaling pathways implicated in the pathogenesis of atherosclerosis and the advancements in research on TCM extracts for prevention and treatment, drawing on original articles from various databases including Google Scholar, Medline, CNKI, Scopus, and Pubmed. The objective is to furnish a reference for the clinical management of cardiovascular diseases.

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“… 1 Atherosclerosis, which is the primary cause of CVD, is influenced by lipids and inflammation. 2 , 3 A lipoprotein called low-density lipoprotein (LDL), which transports cholesterol into peripheral tissue cells, can oxidize to form oxidized LDL, which, when present in excess, increases the risk of atherosclerosis. 4 High-density lipoprotein HDL-cholesterol (HDL-C), on the other hand, acts as a preventative measure against atherosclerosis by moving cholesterol from bodily tissues to the liver, lowering the level of free cholesterol in plasma HDL, and minimizing the deposition of cholesterol in tissues.…”

Section: Introductionmentioning

confidence: 99%

Association of Neutrophil to High-Density Lipoprotein Cholesterol Ratio with Cardiac Ultrasound Parameters and Cardiovascular Risk: A Cross-Sectional Study Based on Healthy Populations

Pan¹,

Zhang²,

Ban³

et al. 2023

JIR

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Background: Neutrophils and high-density lipoprotein cholesterol (HDL-C) are significantly linked to cardiovascular disease (CVD). This study investigates the correlation of neutrophil count to HDL-C ratio (NHR) with cardiac ultrasound parameters and cardiovascular risk in healthy populations. Materials and Methods: Firstly, NHR was calculated based on neutrophils and HDL-C. Then, the differences in basic clinical characteristics and cardiac ultrasound parameters were compared between the high and low NHR groups, males and females. Subsequently, cardiovascular risk was predicted according to the Chinese 10-year ischemic cardiovascular disease (ICVD) risk assessment tool for people aged 35-60 years. Finally, the correlation between NHR and cardiac ultrasound parameters and cardiovascular risk was calculated. Results: A total of 3020 healthy participants, 1879 males and 1141 females, were included. Participants in the high NHR group had significantly increased Aorta (AO), Left Atrium (LA), Right Atrium (RA), Right Ventricle (RV), End Systolic Diameter of Left Ventricle (ESD), End Diastolic Diameter of Left Ventricle (EDD), Main Pulmonary Artery (MPA), Right Ventricular Outflow Tract (RVOT), Interventricular Septum (IVS), Left Ventricular Posterior Wall (LVPW), and cardiovascular risk and decreased E/A values compared to those in the low NHR group. The same results were found in males participants compared to females. A total of 1670 participants underwent ICVD risk assessment tool. Cardiovascular risk was significantly higher in those with high NHR and in males than in those with low NHR and in females. Correlation analysis showed that NHR was positively correlated with AO, LA, RA, RV, ESD, EDD, MPA, RVOT, IVS, LVPW and cardiovascular risk, and negatively correlated with E/A values. Conclusion: Our study demonstrates that NHR is significantly associated with cardiac ultrasound parameters and cardiovascular risk in healthy populations. NHR may serve as a useful indicator for the early diagnosis and treatment of cardiovascular disease among healthy populations.

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Focus on Atherosclerosis and Lipids

Cited by 5 publications

References 26 publications

Foam Cell Targeted Liposomes Co-Encapsulating Superoxide Dismutase and Catalase to Attenuate Atherosclerosis by Inhibiting Oxidative Stress

Foam Cell Targeted Liposomes Co-Encapsulating Superoxide Dismutase and Catalase to Attenuate Atherosclerosis by Inhibiting Oxidative Stress

Modulation of atherosclerosis‐related signaling pathways by Chinese herbal extracts: Recent evidence and perspectives

Association of Neutrophil to High-Density Lipoprotein Cholesterol Ratio with Cardiac Ultrasound Parameters and Cardiovascular Risk: A Cross-Sectional Study Based on Healthy Populations

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