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  1. Book: Atherosclerosis

    Ramji, Dipak P.

    methods and protocols

    (Methods in molecular biology ; 2419 ; Springer protocols)

    2022  

    Author's details edited by Dipak P. Ramji
    Series title Methods in molecular biology ; 2419
    Springer protocols
    Collection
    Keywords Atherosclerosis
    Subject code 616.136
    Language English
    Size xxii, 880 Seiten, Illustrationen, Diagramme, 26 cm
    Publisher Humana Press
    Publishing place New York, NY
    Publishing country United States
    Document type Book
    HBZ-ID HT021277981
    ISBN 978-1-0716-1923-0 ; 9781071619247 ; 1-0716-1923-3 ; 1071619241
    Database Catalogue ZB MED Medicine, Health

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  2. Article ; Online: Monitoring Modified Lipoprotein Uptake and Macropinocytosis Associated with Macrophage Foam Cell Formation.

    Alahmadi, Alaa / Ramji, Dipak P

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2419, Page(s) 247–255

    Abstract: Macrophage foam cell formation plays a crucial role in the initiation and progression of atherosclerosis. Macrophages uptake native and modified low density lipoprotein (LDL) through either receptor-dependent or receptor-independent mechanisms to ... ...

    Abstract Macrophage foam cell formation plays a crucial role in the initiation and progression of atherosclerosis. Macrophages uptake native and modified low density lipoprotein (LDL) through either receptor-dependent or receptor-independent mechanisms to transform into lipid laden foam cells. Foam cells are involved in the formation of fatty streak that is seen during the early stages of atherosclerosis development and therefore represents a promising therapeutic target. Normal or modified lipoproteins labeled with fluorescent dyes such as 1,1'-dioctadecyl-3-3-3',3'-tetramethylindocarbocyanine perchlorate (Dil) are often used to monitor their internalization during foam cell formation. In addition, the fluorescent dye Lucifer Yellow (LY) is widely used as a marker for macropinocytosis activity. In this chapter, we describe established methods for monitoring modified lipoprotein uptake and macropinocytosis during macrophage foam cell formation.
    MeSH term(s) Atherosclerosis ; Foam Cells ; Humans ; Lipoproteins, LDL ; Macrophages ; Pinocytosis
    Chemical Substances Lipoproteins, LDL
    Language English
    Publishing date 2022-03-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1924-7_14
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Investigation of Mitochondrial Bioenergetic Profile and Dysfunction in Atherosclerosis.

    Chan, Yee-Hung / Ramji, Dipak P

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2419, Page(s) 301–311

    Abstract: Mitochondrial function and activity are key indicators of overall cell health and mitochondrial dysfunction is closely associated with disruptions in normal cellular function. Altered mitochondrial function and cellular metabolism has been implicated in ... ...

    Abstract Mitochondrial function and activity are key indicators of overall cell health and mitochondrial dysfunction is closely associated with disruptions in normal cellular function. Altered mitochondrial function and cellular metabolism has been implicated in processes involved in ageing and associated pathologies. In atherosclerosis, compromised mitochondrial respiration can promote plaque instability and other processes that encourage pathogenesis and dysfunction. For example, increasing respiration promotes vascular smooth muscle cell (VSMC) proliferation and attenuates macrophage and VSMC apoptosis. Use of Agilent Seahorse technology to study mitochondrial bioenergetics has largely replaced previous outdated methods which provided limited insight into mitochondrial function and were associated with various issues. This chapter describes the use of Seahorse Agilent technology (Mito Stress Test) to study key parameters of mitochondrial respiration on cultured cells relevant to atherosclerosis.
    MeSH term(s) Atherosclerosis/metabolism ; Cells, Cultured ; Energy Metabolism/physiology ; Humans ; Mitochondria/metabolism ; Plaque, Atherosclerotic/metabolism
    Language English
    Publishing date 2022-03-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1924-7_19
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Key Roles of Inflammation in Atherosclerosis: Mediators Involved in Orchestrating the Inflammatory Response and Its Resolution in the Disease Along with Therapeutic Avenues Targeting Inflammation.

    Chan, Yee-Hung / Ramji, Dipak P

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2419, Page(s) 21–37

    Abstract: Inflammation is a critical driver of all stages of atherosclerosis, from lesion development to plaque rupture. Cytokines are mediators of the immune response and in atherosclerosis, the balance of anti- and pro-inflammatory cytokines is tipped in favor ... ...

    Abstract Inflammation is a critical driver of all stages of atherosclerosis, from lesion development to plaque rupture. Cytokines are mediators of the immune response and in atherosclerosis, the balance of anti- and pro-inflammatory cytokines is tipped in favor of the latter, resulting in persistent and unresolved inflammation. Although reducing plasma cholesterol levels mainly via the use of statins has positively impacted patient outcomes and reduced mortality rates, the presence of significant residual inflammation and cardiovascular risk posttherapy emphasizes the prevailing risk of primary and secondary events driven by inflammation independently of hyperlipidemia. Given the dominant role of inflammation in driving pathogenesis, alternative therapeutic avenues beyond targeting lowering of plasma lipids are required. This chapter will discuss the role of inflammation and pro-inflammatory cytokines in driving atherogenesis and disease progression, the therapeutic potential of targeting cytokines for atherosclerosis and promising avenues in this area.
    MeSH term(s) Atherosclerosis/pathology ; Cytokines ; Humans ; Inflammation/complications ; Inflammation/drug therapy ; Inflammation/pathology ; Inflammation Mediators ; Plaque, Atherosclerotic/drug therapy
    Chemical Substances Cytokines ; Inflammation Mediators
    Language English
    Publishing date 2022-03-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1924-7_2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Atherosclerosis: Pathogenesis and Key Cellular Processes, Current and Emerging Therapies, Key Challenges, and Future Research Directions.

    Chan, Yee-Hung / Ramji, Dipak P

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2419, Page(s) 3–19

    Abstract: Atherosclerosis is the principal cause of cardiovascular disease that continues to be a substantial drain on healthcare systems, being responsible for about 31% of all global deaths. Atherogenesis is influenced by a range of factors, including oxidative ... ...

    Abstract Atherosclerosis is the principal cause of cardiovascular disease that continues to be a substantial drain on healthcare systems, being responsible for about 31% of all global deaths. Atherogenesis is influenced by a range of factors, including oxidative stress, inflammation, hypertension, and hyperlipidemia, and is ultimately driven by the accumulation of low-density lipoprotein cholesterol within the arterial wall of medium and large arteries. Lipoprotein accumulation stimulates the infiltration of immune cells (such as monocytes/macrophages and T-lymphocytes), some of which take up the lipoprotein, leading to the formation of lipid-laden foam cells. Foam cell death results in increased accumulation of dead cells, cellular debris and extracellular cholesterol, forming a lipid-rich necrotic core. Vascular smooth muscle cells from the arterial media also migrate into the intima layer and proliferate, taking up the available lipids to become foam cells and producing extracellular matrix proteins such as collagen and elastin. Plaque progression is characterized by the formation of a fibrous cap composed of extracellular matrix proteins and smooth muscle cells, which acts to stabilize the atherosclerotic plaque. Degradation, thinning, and subsequent rupture of the fibrous cap leads to lumen-occlusive atherothrombosis, most commonly resulting in heart attack or stroke. This chapter describes the pathogenesis of atherosclerosis, current and emerging therapies, key challenges, and future directions of research.
    MeSH term(s) Arteries ; Atherosclerosis/etiology ; Atherosclerosis/therapy ; Foam Cells/pathology ; Humans ; Inflammation/pathology ; Plaque, Atherosclerotic/pathology
    Language English
    Publishing date 2022-03-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1924-7_1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Probing Inflammasome Activation in Atherosclerosis.

    Chan, Yee-Hung / Ramji, Dipak P

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2419, Page(s) 313–331

    Abstract: Atherosclerosis is driven by chronic inflammation in all stages of the disease. Inflammation is fueled by elevated levels of pro-inflammatory cytokines. Interleukins (IL) are cytokines of particular importance in atherosclerosis, due to their key ... ...

    Abstract Atherosclerosis is driven by chronic inflammation in all stages of the disease. Inflammation is fueled by elevated levels of pro-inflammatory cytokines. Interleukins (IL) are cytokines of particular importance in atherosclerosis, due to their key involvement in various pro-atherogenic processes, including infiltration of immune cells to the lesion, stimulation of the production of other pro-inflammatory mediators by other sources, and generation of lipid laden foam cells, all of which contribute to plaque development and progression. Various stimuli that are abundant in atherosclerotic plaques, including oxidized low-density lipoprotein, cholesterol crystals and reactive oxygen species can trigger inflammasome activation. Importantly, activation of the nucleotide oligomerization domain leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome activates the caspase-1 protease and results in the generation and release of potent pro-inflammatory cytokines, IL-1β and IL-18. Both cytokines are influential in driving chronic inflammation and atherogenesis. This chapter describes the use of enzyme-linked immunosorbent assay (ELISA) and Western blot to quantify these cytokines in cell supernatant and lysate respectively, after stimulating inflammasome activation in cultured cells.
    MeSH term(s) Atherosclerosis/pathology ; Caspase 1/metabolism ; Humans ; Inflammasomes/metabolism ; Interleukin-1beta/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Plaque, Atherosclerotic
    Chemical Substances Inflammasomes ; Interleukin-1beta ; NLR Family, Pyrin Domain-Containing 3 Protein ; Caspase 1 (EC 3.4.22.36)
    Language English
    Publishing date 2022-03-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1924-7_20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The Role of Punicalagin and Its Metabolites in Atherosclerosis and Risk Factors Associated with the Disease.

    Alalawi, Sulaiman / Albalawi, Faizah / Ramji, Dipak P

    International journal of molecular sciences

    2023  Volume 24, Issue 10

    Abstract: Atherosclerotic cardiovascular disease (ACVD) is the leading cause of death worldwide. Although current therapies, such as statins, have led to a marked reduction in morbidity and mortality from ACVD, they are associated with considerable residual risk ... ...

    Abstract Atherosclerotic cardiovascular disease (ACVD) is the leading cause of death worldwide. Although current therapies, such as statins, have led to a marked reduction in morbidity and mortality from ACVD, they are associated with considerable residual risk for the disease together with various adverse side effects. Natural compounds are generally well-tolerated; a major recent goal has been to harness their full potential in the prevention and treatment of ACVD, either alone or together with existing pharmacotherapies. Punicalagin (PC) is the main polyphenol present in pomegranates and pomegranate juice and demonstrates many beneficial actions, including anti-inflammatory, antioxidant, and anti-atherogenic properties. The objective of this review is to inform on our current understanding of the pathogenesis of ACVD and the potential mechanisms underlying the beneficial actions of PC and its metabolites in the disease, including the attenuation of dyslipidemia, oxidative stress, endothelial cell dysfunction, foam cell formation, and inflammation mediated by cytokines and immune cells together with the regulation of proliferation and migration of vascular smooth muscle cells. Some of the anti-inflammatory and antioxidant properties of PC and its metabolites are due to their strong radical-scavenging activities. PC and its metabolites also inhibit the risk factors of atherosclerosis, including hyperlipidemia, diabetes mellitus, inflammation, hypertension, obesity, and non-alcoholic fatty liver disease. Despite the promising findings that have emerged from numerous in vitro, in vivo, and clinical studies, deeper mechanistic insights and large clinical trials are required to harness the full potential of PC and its metabolites in the prevention and treatment of ACVD.
    MeSH term(s) Humans ; Antioxidants/therapeutic use ; Antioxidants/pharmacology ; Atherosclerosis/drug therapy ; Atherosclerosis/pathology ; Risk Factors ; Inflammation ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use
    Chemical Substances punicalagin (65995-63-3) ; Antioxidants ; Anti-Inflammatory Agents
    Language English
    Publishing date 2023-05-09
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24108476
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: The Beneficial Effects of Pine Nuts and Its Major Fatty Acid, Pinolenic Acid, on Inflammation and Metabolic Perturbations in Inflammatory Disorders.

    Takala, Rabaa / Ramji, Dipak P / Choy, Ernest

    International journal of molecular sciences

    2023  Volume 24, Issue 2

    Abstract: Inflammatory disorders such as atherosclerosis, diabetes and rheumatoid arthritis are regulated by cytokines and other inflammatory mediators. Current treatments for these conditions are associated with significant side effects and do not completely ... ...

    Abstract Inflammatory disorders such as atherosclerosis, diabetes and rheumatoid arthritis are regulated by cytokines and other inflammatory mediators. Current treatments for these conditions are associated with significant side effects and do not completely suppress inflammation. The benefits of diet, especially the role of specific components, are poorly understood. Polyunsaturated fatty acids (PUFAs) have several beneficial health effects. The majority of studies on PUFAs have been on omega-3 fatty acids. This review will focus on a less studied fatty acid, pinolenic acid (PNLA) from pine nuts, which typically constitutes up to 20% of its total fatty acids. PNLA is emerging as a dietary PUFA and a promising supplement in the prevention of inflammatory disorders or as an alternative therapy. Some studies have shown the health implications of pine nuts oil (PNO) and PNLA in weight reduction, lipid-lowering and anti-diabetic actions as well as in suppression of cell invasiveness and motility in cancer. However, few reviews have specifically focused on the biological and anti-inflammatory effects of PNLA. Furthermore, in recent bioinformatic studies on human samples, the expression of many mRNAs and microRNAs was regulated by PNLA indicating potential transcriptional and post-transcriptional regulation of inflammatory and metabolic processes. The aim of this review is to summarize, highlight, and evaluate research findings on PNO and PNLA in relation to potential anti-inflammatory benefits and beneficial metabolic changes. In this context, the focus of the review is on the potential actions of PNLA on inflammation along with modulation of lipid metabolism and oxidative stress based on data from both in vitro and in vivo experiments, and human findings, including gene expression analysis.
    MeSH term(s) Humans ; Nuts ; Inflammation/drug therapy ; Linolenic Acids/pharmacology ; Linolenic Acids/therapeutic use ; Fatty Acids, Unsaturated/therapeutic use ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Fatty Acids, Omega-3/therapeutic use
    Chemical Substances 5,9,12-octadecatrienoic acid (13237-97-3) ; Linolenic Acids ; Fatty Acids, Unsaturated ; Anti-Inflammatory Agents ; Fatty Acids, Omega-3
    Language English
    Publishing date 2023-01-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24021171
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: A perspective on targeting inflammation and cytokine actions in atherosclerosis.

    Chan, Yee-Hung / Ramji, Dipak P

    Future medicinal chemistry

    2020  Volume 12, Issue 7, Page(s) 613–626

    Abstract: Atherosclerosis, a chronic inflammatory disorder of the vasculature that results in cardiovascular disease, continues to pose a significant health and economic burden on modern society. Whilst inflammation has generally been accepted as the key driver of ...

    Abstract Atherosclerosis, a chronic inflammatory disorder of the vasculature that results in cardiovascular disease, continues to pose a significant health and economic burden on modern society. Whilst inflammation has generally been accepted as the key driver of all stages of the disease, it was not until recently that inhibition of a specific proinflammatory cytokine (IL-1β) yielded successful results in the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study trial. This article offers a perspective on targeting inflammation for atherosclerosis, focusing on results of recent Phase III clinical trials, and discusses other potential candidates together with future challenges and prospects.
    MeSH term(s) Anti-Inflammatory Agents/pharmacology ; Atherosclerosis/drug therapy ; Atherosclerosis/immunology ; Clinical Trials, Phase II as Topic ; Humans ; Inflammation/drug therapy ; Inflammation/immunology ; Interleukin-1beta/antagonists & inhibitors ; Interleukin-1beta/immunology
    Chemical Substances Anti-Inflammatory Agents ; IL1B protein, human ; Interleukin-1beta
    Language English
    Publishing date 2020-03-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 1756-8927
    ISSN (online) 1756-8927
    DOI 10.4155/fmc-2019-0301
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Evaluation of Plaque Burden and Lipid Content in Atherosclerotic Plaques.

    Chan, Yee-Hung / Alahmadi, Alaa / Alotibi, Reem / Ramji, Dipak P

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2419, Page(s) 481–496

    Abstract: Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid-rich, fibrous plaques within the arterial wall of medium and large arteries. Plaques prone to rupture are typically rich in lipids and pro-inflammatory markers. ... ...

    Abstract Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid-rich, fibrous plaques within the arterial wall of medium and large arteries. Plaques prone to rupture are typically rich in lipids and pro-inflammatory markers. Cells within the plaque can take up lipids via different mechanisms leading to the formation and accumulation of lipid-rich foam cells, a key hallmark of the disease. Evaluation of plaque burden and lipid content is hence important to determine disease progression and severity. This chapter describes the most commonly used staining methods that enable visualization and analysis of mouse atherosclerotic plaques. These methods include en face preparation of mouse aorta, and staining sections of arteries using hematoxylin and eosin, Oil Red O, and Masson's Trichrome.
    MeSH term(s) Animals ; Aorta ; Atherosclerosis ; Hematoxylin ; Lipids/analysis ; Mice ; Plaque, Atherosclerotic
    Chemical Substances Lipids ; Hematoxylin (YKM8PY2Z55)
    Language English
    Publishing date 2022-03-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1924-7_29
    Database MEDical Literature Analysis and Retrieval System OnLINE

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