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1.
Curr Atheroscler Rep ; 26(7): 289-304, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38805145

RESUMO

PURPOSE OF REVIEW: In this review, we explore the intriguing and evolving connections between bacterial extracellular membrane nanovesicles (BEMNs) and atherosclerosis development, highlighting the evidence on molecular mechanisms by which BEMNs can promote the athero-inflammatory process that is central to the progression of atherosclerosis. RECENT FINDINGS: Atherosclerosis is a chronic inflammatory disease primarily driven by metabolic and lifestyle factors; however, some studies have suggested that bacterial infections may contribute to the development of both atherogenesis and inflammation in atherosclerotic lesions. In particular, the participation of BEMNs in atherosclerosis pathogenesis has attracted special attention. We provide some general insights into how the immune system responds to potential threats such as BEMNs during the development of atherosclerosis. A comprehensive understanding of contribution of BEMNs to atherosclerosis pathogenesis may lead to the development of targeted interventions for the prevention and treatment of the disease.


Assuntos
Aterosclerose , Vesículas Extracelulares , Aterosclerose/microbiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Humanos , Vesículas Extracelulares/metabolismo , Animais , Inflamação/metabolismo , Bactérias/metabolismo , Infecções Bacterianas/microbiologia , Infecções Bacterianas/complicações , Infecções Bacterianas/metabolismo
2.
Curr Med Chem ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38529605

RESUMO

ATP-binding cassette transporter A1 (ABCA1) is one of the key proteins regulating cholesterol homeostasis and playing a crucial role in atherosclerosis development. ABCA1 regulates the rate-limiting step of reverse cholesterol transport, facilitates the efflux of surplus intracellular cholesterol and phospholipids, and suppresses inflammation through several signalling pathways. At the same time, many mutations and Single Nucleotide Polymorphisms (SNPs) have been identified in the ABCA1 gene, which affects its biological function and is associated with several hereditary diseases (such as familial hypo-alpha-lipoproteinaemia and Tangier disease) and increased risk of cardiovascular diseases (CVDs). This review summarises recently identified mutations and SNPs in their connection to atherosclerosis and associated CVDs. Also, we discuss the recently described application of various plant-derived compounds to modulate ABCA1 expression in different in vitro and in vivo models. Herein, we present a comprehensive overview of the association of ABCA1 mutations and SNPs with CVDs and as a pharmacological target for different natural-derived compounds and highlight the potential application of these phytochemicals for treating atherosclerosis through modulation of ABCA1 expression.

3.
Curr Med Chem ; 28(12): 2438-2450, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32867633

RESUMO

The most typical feature of atherogenesis in humans at its early stage is the formation of foam cells in subendothelial arterial intima, which occurs as the consequence of intracellular cholesterol deposition. The main source of lipids accumulating in the arterial wall is circulating low-density lipoprotein (LDL). However, LDL particles should undergo proatherogenic modification to acquire atherogenic properties. One of the known types of atherogenic modification of LDL is enzymatic deglycosilation, namely, desialylation, which is the earliest change in the cascade of following multiple LDL modifications. The accumulating data make sialidases an intriguing and plausible therapeutic target, since pharmacological modulation of activity of these enzymes may have beneficial effects in several pathologies, including atherosclerosis. The hypothesis exists that decreasing LDL enzymatic desialylation may result in the prevention of lipid accumulation in arterial wall, thus breaking down one of the key players in atherogenesis at the cellular level. Several drugs acting as glycomimetics and inhibiting sialidase enzymatic activity already exist, but the concept of sialidase inhibition as an anti-atherosclerosis strategy remains unexplored to date. This review is focused on the potential possibilities of the repurposing of sialidase inhibitors for pathogenetic anti-atherosclerotic therapy.


Assuntos
Aterosclerose , Neuraminidase , Aterosclerose/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Humanos , Lipoproteínas LDL
4.
Int J Mol Sci ; 21(15)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32751832

RESUMO

Immunoglobulins are the potent effector proteins of the humoral immune response. In the course of evolution, immunoglobulins have formed extremely diverse types of molecular structures with antigen-recognizing, antigen-binding, and effector functions embedded in a single molecule. Polysaccharide moiety of immunoglobulins plays the essential role in immunoglobulin functioning. There is growing evidence that the carbohydrate composition of immunoglobulin-linked glycans, and especially their terminal sialic acid residues, provide a key effect on the effector functions of immunoglobulins. Possibly, sialylation of Fc glycan is a common mechanism of IgG anti-inflammatory action in vivo. Thus, the post-translational modification (glycosylation) of immunoglobulins opens up significant possibilities in the diagnosis of both immunological and inflammatory disorders and in their therapies. This review is focused on the analysis of glycosylation of immunoglobulins, which can be a promising addition to improve existing strategies for the diagnosis and treatment of various immuno-inflammatory diseases.


Assuntos
Doenças do Sistema Imunitário/tratamento farmacológico , Fragmentos Fc das Imunoglobulinas/química , Imunoglobulina G , Inflamação/tratamento farmacológico , Ácido N-Acetilneuramínico/química , Polissacarídeos/química , Animais , Glicosilação , Humanos , Imunoglobulina G/química , Imunoglobulina G/uso terapêutico , Camundongos , Processamento de Proteína Pós-Traducional
5.
Biology (Basel) ; 9(8)2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32708035

RESUMO

Desialylation-loss of terminal sialic acid residues from glycoconjugates catalyzed by sialidases-is involved in many human diseases and is considered a key molecular event of atherosclerosis onset. Desialylated low-density lipoproteins with atherogenic properties have been detected in human blood previously. However, there is currently no consensus on the origin of desialylation activity in the bloodstream. Here, we suggest viral intervention as a possible explanation. In order to address our hypothesis, we studied seasonal patterns of blood serum sialidase enzymatic activity and designed an approach to detect and quantify viral sialidase genetic presence. Increased sialidase activity in autumn-winter combined with detectable levels of influenza virus sialidase mRNA suggests exogenous viral sialidase as a viable component of desialylation in human blood, providing new insights on the molecular background of atherogenesis.

6.
Curr Drug Targets ; 20(9): 938-941, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30848200

RESUMO

Atherosclerosis is associated with the increased trans-sialidase activity, which can be detected in the blood plasma of atherosclerosis patients. The likely involvement in the disease pathogenesis made this activity an interesting research subject and the enzyme that may perform such activity was isolated and characterized in terms of substrate specificity and enzymatic properties. It was found that the enzyme has distinct optimum pH values, and its activity was enhanced by the presence of Ca2+ ions. Most importantly, the enzyme was able to cause atherogenic modification of lowdensity lipoprotein (LDL) particles in vitro. However, the identity of the discovered enzyme remained to be defined. Currently, sialyltransferases, mainly ST6Gal I, are regarded as major contributors to sialic acid metabolism in human blood. In this mini-review, we discuss the possibility that atherosclerosis- associated trans-sialidase does, in fact, belong to the sialyltransferases family.


Assuntos
Aterosclerose/enzimologia , Ácido N-Acetilneuramínico/sangue , Sialiltransferases/metabolismo , Animais , Aterosclerose/metabolismo , Cálcio/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Lipoproteínas LDL/metabolismo , Sialiltransferases/sangue , Especificidade por Substrato
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