Molecular Pharmacology of Inflammation Resolution in Atherosclerosis

Kotlyarov, Stanislav; Kotlyarova, Anna

doi:10.3390/ijms23094808

Cited by 14 publications

(8 citation statements)

References 318 publications

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“…117 An holistic approach to treat inflammatory vasculopathy and unresolved inflammation has been proposed in diseases other than SCD such as in cardiovascular disease or atherosclerosis by administrating ω-3 fatty acids (ω-3 PUFAs). [118][119][120] Previous studies in both mouse models and patients with SCD have shown beneficial effects of dietary supplementation with ω-3 PUFAs preparations. [121][122][123][124] As shown in Table 1, two clinical studies with omega(ω)-3 fatty acid supplementation are actively recruiting SCD patients.…”

Section: Agents Targeting the Hemolysis-vascular Endothelial Axismentioning

confidence: 99%

Novel therapeutic approaches in thalassemias, sickle cell disease, and other red cell disorders

Pinto,

Mazzi,

De Franceschi

2024

Blood

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In this last decade, a deeper understanding of the pathophysiology of hereditary red cell disorders and the development of novel classes of pharmacologic agents have provided novel therapeutic approaches to thalassemias, sickle cell disease (SCD) and other red cell disorders. Here, we analyze and discuss the novel therapeutic options according to their targets and taking into consideration the complex process of erythroid differentiation, maturation, and survival of erythrocytes in the peripheral circulation. We focus on active clinical exploratory and confirmatory trials on thalassemias, SCD and other red cell disorders. Beside -thalassemia and SCD, we found that the development of new therapeutic strategies has allowed the design of clinic studies also for hereditary red cell disorders still lacking valuable therapeutic alternative such as -thalassemias, congenital dyserythropoietic anemia or Blackfan Diamond anemia. In addition, reduction of heme synthesis, which can be achieved by the repurposed anti-psychotic drug Bitopertin, might affect not only hematological disorders but multiorgan diseases such as erythropoietic protoporphyria. Finally, our review highlights the current state of therapeutic scenarios, in which multiple indications targeting different red cell disorders are being considered for a single agent. This is welcome change which will hopefully expand therapeutic option for patients affected by thalassemias, SCD and other red cell disorders.

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Section: Agents Targeting the Hemolysis-vascular Endothelial Axismentioning

confidence: 99%

Novel therapeutic approaches in thalassemias, sickle cell disease, and other red cell disorders

Pinto,

Mazzi,

De Franceschi

2024

Blood

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“…These lipids activate immune cells that trigger a continuous secretion of pro-inflammatory factors and adhesive molecules (VCAM and ICAM). These latter provoke the sustained recruitment of immune cells in the endothelium and enhance the formation of atherosclerotic plaques [ 182 ]. In coronary artery diseases, diverse mechanisms, such as immune complex-mediated and cell-mediated inflammation, contribute to its growth [ 181 ].…”

Section: Designed Polyphenolic-loaded Nanocarriers For Inflammation-m...mentioning

confidence: 99%

Modulating Inflammation-Mediated Diseases via Natural Phenolic Compounds Loaded in Nanocarrier Systems

2023

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The global increase and prevalence of inflammatory-mediated diseases have been a great menace to human welfare. Several works have demonstrated the anti-inflammatory potentials of natural polyphenolic compounds, including flavonoid derivatives (EGCG, rutin, apigenin, naringenin) and phenolic acids (GA, CA, etc.), among others (resveratrol, curcumin, etc.). In order to improve the stability and bioavailability of these natural polyphenolic compounds, their recent loading applications in both organic (liposomes, micelles, dendrimers, etc.) and inorganic (mesoporous silica, heavy metals, etc.) nanocarrier technologies are being employed. A great number of studies have highlighted that, apart from improving their stability and bioavailability, nanocarrier systems also enhance their target delivery, while reducing drug toxicity and adverse effects. This review article, therefore, covers the recent advances in the drug delivery of anti-inflammatory agents loaded with natural polyphenolics by the application of both organic and inorganic nanocarriers. Even though nanocarrier technology offers a variety of possible anti-inflammatory advantages to naturally occurring polyphenols, the complexes’ inherent properties and mechanisms of action have not yet been fully investigated. Thus, expanding the quest on novel natural polyphenolic-loaded delivery systems, together with the optimization of complexes’ activity toward inflammation, will be a new direction of future efforts.

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“…Resolution of Inflammation (RoI) is not a passive process but indeed a dynamic phenomenon, finely tuned by several soluble mediators, including the so called Specialised Pro-resolving Mediators (SPMs), such as Lipoxins (LXs), Resolvins, Protectins, and Maresins ( Kotlyarov and Kotlyarova, 2022 ). Thanks to the ground-breaking work of Godson and collaborators, our group has been mainly focusing on elucidating the role of LXs in RoI and as a novel therapeutic target.…”

Section: Atherosclerosis: the ‘Silent Killer’ Of The 21st Centurymentioning

confidence: 99%

“…The ROS molecules present in the inflammatory milieu elicit in vivo and in vitro lipid peroxidation, wherein there is oxidative decomposition of omega-3 and -6 polyunsaturated fats of phospholipids for LX production. Research suggests that arachidonic acid is a vital LDL present as an endogenous phospholipid in biological membranes or through dietary supply of linoleic acid or animal protein ( Kotlyarov and Kotlyarova, 2022 ). With the resolution of inflammation being a driving factor in atherosclerosis prevalence and development, there is growing consensus into the potential role that synthetic lipoxin mimetics may possess as a future treatment for this disease.…”

Section: Novel Targets In the Resolution Of Atherosclerosismentioning

confidence: 99%

Posing the rationale for synthetic lipoxin mimetics as an adjuvant treatment to gold standard atherosclerosis therapies

Millar

Gaetano²

2023

Front. Pharmacol.

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Atherosclerosis is a progressive, multifactorial inflammatory, and dyslipidaemic disease, responsible for the majority of cardiovascular diseases globally. The chronic inflammation is the main driver of the initiation and progression of such disease, as a result of an imbalanced lipid metabolism and an ineffective immune response to attenuate the inflammatory component. The importance of inflammation resolution is being increasingly recognised in atherosclerosis and cardiovascular disease. It has a complex mechanism consisting of multiple stages, including restoring an effective removal of apoptotic bodies (efferocytosis) and their degradation (effero-metabolism), a macrophage phenotype switching towards resolving phenotypes, and the promotion of tissue healing and regeneration. The low-grade inflammation associated with atherosclerosis development is a driving force in disease exacerbation, and hence inflammation resolution is a key area of research. In this review, we explore the complex disease pathogenesis and its many contributing factors to gain a greater understanding of the disease and identify the current and potential therapeutic targets. First-line treatments and their efficacy will also be discussed in detail, to highlight the emerging field of resolution pharmacology. Despite the great efforts made by current gold-standard treatments, such as lipid-lowering and glucose-lowering drugs, they remain ineffective at tackling residual inflammatory risk and residual cholesterol risk. Resolution pharmacology represents a new era of atherosclerosis therapy, as endogenous ligands associated with inflammation resolution are exploited for their pharmacological benefits in a more potent and longer-acting manner. Novel FPR2-agonists, such as synthetic lipoxin analogues, provide an exciting new approach to enhance the pro-resolving response of the immune system and subsequently end the pro-inflammatory response to allow for an anti-inflammatory and pro-resolving environment for tissue healing, regeneration, and return to homeostasis.

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Molecular Pharmacology of Inflammation Resolution in Atherosclerosis

Cited by 14 publications

References 318 publications

Novel therapeutic approaches in thalassemias, sickle cell disease, and other red cell disorders

Novel therapeutic approaches in thalassemias, sickle cell disease, and other red cell disorders

Modulating Inflammation-Mediated Diseases via Natural Phenolic Compounds Loaded in Nanocarrier Systems

Posing the rationale for synthetic lipoxin mimetics as an adjuvant treatment to gold standard atherosclerosis therapies

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