PCSK9 inhibition, LDL and lipopolysaccharides: a complex and "dangerous" relationship

Feminò, Raimondo; Feminò, Giovanni; Cavezzi, Attilio; Troiani, Emidio

doi:10.23736/s0392-9590.21.04632-0

Cited by 3 publications

(4 citation statements)

References 123 publications

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“…Lipid A then initiates a signaling cascade resulting in activation of various proinflammatory pathways (predominantly NF-κB) and increases oxidative stress upon binding to Toll-Like Receptor 4 (TLR4) (Asehnoune et al, 2004;Boutagy et al, 2016), resulting in systemic and retinal inflammation (Han et al, 2020). Inflammatory LPS has also been identified as probable culprit of cardiovascular atherogenesis (Feminò et al, 2021).…”

Section: The Link Between Dysbiosis Leaky Gut and Inflammationmentioning

confidence: 99%

Gut Microbiome in Retina Health: The Crucial Role of the Gut-Retina Axis

Scuderi

Troiani²,

Minnella

2022

Front. Microbiol.

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The term microbiome means not only a complex ecosystem of microbial species that colonize our body but also their genome and the surrounding environment in which they live. Recent studies support the existence of a gut-retina axis involved in the pathogenesis of several chronic progressive ocular diseases, including age-related macular disorders. This review aims to underline the importance of the gut microbiome in relation to ocular health. After briefly introducing the characteristics of the gut microbiome in terms of composition and functions, the role of gut microbiome dysbiosis, in the development or progression of retinal diseases, is highlighted, focusing on the relationship between gut microbiome composition and retinal health based on the recently investigated gut-retina axis.

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Section: The Link Between Dysbiosis Leaky Gut and Inflammationmentioning

confidence: 99%

Gut Microbiome in Retina Health: The Crucial Role of the Gut-Retina Axis

Scuderi

Troiani²,

Minnella

2022

Front. Microbiol.

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“…Similarly, based on the mesenteric vein-portal vein system, metabolites in the gut are absorbed and transported directly to the liver through the gut mucosa and then transformed into metabolic raw materials and regulatory molecules. SCFA ( 14 ), secondary bile acid (SBA) ( 15 ), TMAO ( 16 ) and LPS ( 17 ) are main MDMs that can significantly regulate the cholesterol metabolism and even reduce LDL-C through the gut-liver axis. Thus, the gut microbiota and metabolites play key roles in regulating LDL-C levels.…”

Section: Microbial Effects On Cholesterol Metabolismmentioning

confidence: 99%

“…Another meta-analysis showed that the translocation of LPS was directly related to the concentration of LDL-C, which was more pronounced in smokers or obese individuals ( 97 , 98 ). LPS promotes hepatic proprotein convertase subtilisin/kexin-9 (PCSK9) synthesis that suppresses cholesterol consumption by binding to LDL-C receptors on cell membranes ( 17 , 99 ). The mechanism by which LPS increases the synthesis of PCSK9 in the liver may be related to the phosphatidylinositol-3-kinase (PI3K)-Akt signaling pathway; further studies are required in this regard ( 100 ).…”

Section: Points Of Contact Between Gut Microbiota and Cholesterol Met...mentioning

confidence: 99%

Targets of statins intervention in LDL-C metabolism: Gut microbiota

Sun

Wang

et al. 2022

Front. Cardiovasc. Med.

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Increasing researches have considered gut microbiota as a new “metabolic organ,” which mediates the occurrence and development of metabolic diseases. In addition, the liver is an important organ of lipid metabolism, and abnormal lipid metabolism can cause the elevation of blood lipids. Among them, elevated low-density lipoprotein cholesterol (LDL-C) is related with ectopic lipid deposition and metabolic diseases, and statins are widely used to lower LDL-C. In recent years, the gut microbiota has been shown to mediate statins efficacy, both in animals and humans. The effect of statins on microbiota abundance has been deeply explored, and the pathways through which statins reduce the LDL-C levels by affecting the abundance of microbiota have gradually been explored. In this review, we discussed the interaction between gut microbiota and cholesterol metabolism, especially the cholesterol-lowering effect of statins mediated by gut microbiota, via AMPK-PPARγ-SREBP1C/2, FXR and PXR-related, and LPS-TLR4-Myd88 pathways, which may help to explain the individual differences in statins efficacy.

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“…Interestingly, Cochrane reviewers also found that sponsored studies yield results that are more favorable towards certain therapies than unsponsored ones, which cannot be explained by standard risk biases 19 ; in addition, a recent cross-sectional study highlighted that 24% of guideline writers had potentially relevant undisclosed ties to pharmaceutical companies 55 . An example of this potential bias is also represented by the guidelines on lipid-lowering medications where contrasting interests tend to conflict, leaving little space to independent and reliable scientific literature 56 .…”

Section: B) Biases In Biomedical Researchmentioning

confidence: 99%

Biomedical science limitations and flaws: why not choose wisely?

Cavezzi¹,

d'Errico²,

Colucci³

2022

JTAVR

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Biomedical science is experiencing a reassessment of its practices of healthcare management where more appropriate cost-benefit profiles are being combined with improvements in knowledge, effectiveness, and safety of diagnostic/therapeutic procedures to drive the advances in medicine. This review aims to assess: (a) possible biases of the scientific literature and research, (b) the clinical value and the cost-effectiveness of the principal medical practices and (c) the possible contribution of integrative and translational medicine. Literature shows that current medical research has cognitive (mostly industry-induced) biases that negatively impact clinical practice: the ever-increasing use of drugs and technologies, united with a certain inattention to the basic mechanisms of pathophysiology are paving the way of reductionism in medical practice. A critical view of innovations in medicine, together with a sound understanding and application of the scientific method, would improve the effectiveness, safety and sustainability of therapies. Translational and integrative medicine can contribute to develop a new patient-centered approach. Conversely, reductionism, eminence/reimbursement-based medical decisions, lack of patient education, industry-influenced science, and limited awareness from physicians may compromise the efficacy, safety, appropriateness, and cost-effectiveness of diagnostic and therapeutic processes.

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PCSK9 inhibition, LDL and lipopolysaccharides: a complex and "dangerous" relationship

Cited by 3 publications

References 123 publications

Gut Microbiome in Retina Health: The Crucial Role of the Gut-Retina Axis

Gut Microbiome in Retina Health: The Crucial Role of the Gut-Retina Axis

Targets of statins intervention in LDL-C metabolism: Gut microbiota

Biomedical science limitations and flaws: why not choose wisely?

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