PCSK9 and the Gut-Liver-Brain Axis: A Novel Therapeutic Target for Immune Regulation in Alcohol Use Disorder

Lee, Ji Soo; O’Connell, Emma M.; Pacher, Pál; Lohoff, Falk W.

doi:10.3390/jcm10081758

Cited by 15 publications

(11 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lower levels of circulating PCSK9 in normolipidemic subjects are associated with adipose tissue inflammation, 96 whereas PCSK9 inhibition reduces inflammation in the liver. 97 Additional studies will clearly define the role of PCSK9 as a link between cholesterol and inflammation and how much of the inflammatory response is cholesterol independent.…”

Section: Pcsk9 and Inflammationmentioning

confidence: 99%

Effects of PCSK9 Targeting: Alleviating Oxidation, Inflammation, and Atherosclerosis

Punch

Klein

Diaba-Nuhoho

et al. 2022

JAHA

View full text Add to dashboard Cite

Characterized as a chronic inflammatory disease of the large arteries, atherosclerosis is the primary cause of cardiovascular disease, the leading contributor of morbidity and mortality worldwide. Elevated plasma cholesterol levels and chronic inflammation within the arterial plaque are major mediators of plaque initiation, progression, and instability. In 2003, the protein PCSK9 (proprotein convertase subtilisin/kexin 9) was discovered to play a critical role in cholesterol regulation, thus becoming a key player in the mechanisms behind atherosclerotic plaque development. Emerging evidence suggests that PCSK9 could potentially have effects on atherosclerosis that are independent of cholesterol levels. The objective of this review was to discuss the role on PCSK9 in oxidation, inflammation, and atherosclerosis. This function activates proinflammatory cytokine production and affects oxidative modifications within atherosclerotic lesions, revealing its more significant role in atherosclerosis. Although a variety of evidence demonstrates that PCSK9 plays a role in atherosclerotic inflammation, the direct mechanism of involvement is still unknown, driving a gap in knowledge to such a predominant player in cardiovascular disease. Investigation of proteins structurally related to PCSK9 may interestingly be the link in unveiling the mechanistic role of this protein’s involvement in oxidation and inflammation. Importantly, the unique structure of PCSK9 bears structural homology to a one‐of‐a‐kind domain found in the metabolic protein resistin, which is responsible for many of the same inflammatory outcomes as PCSK9. Closing this gap in knowledge of PCSK9`s role in atherosclerotic oxidation and inflammation will provide fundamental information for understanding, preventing, and treating cardiovascular disease.

show abstract

Section: Pcsk9 and Inflammationmentioning

confidence: 99%

Effects of PCSK9 Targeting: Alleviating Oxidation, Inflammation, and Atherosclerosis

Punch

Klein

Diaba-Nuhoho

et al. 2022

JAHA

View full text Add to dashboard Cite

show abstract

“…In addition, subjects with Alcohol Use Disorders (AUD) show a worse postoperative recovery, a poor response to vaccination or a slower recovery from infections [ 81 ]. CHD alters innate and adaptive immune responses [ 82 , 86 ] and can affect a large number of systems through them, since this type of consumption has been associated with damage to different tissues such as pancreas, liver, gut, circulatory system or nervous system [ 87 ], and there are several studies that attribute, at least in part, a role of persistent systemic and local inflammation in these conditions [ 88 ].…”

Section: Effects Of Alcohol On Immune System: Putting All the Pieces Togethermentioning

confidence: 99%

The Immune System through the Lens of Alcohol Intake and Gut Microbiota

Calleja‐Conde

Echeverry‐Alzate

Bühler

et al. 2021

IJMS

View full text Add to dashboard Cite

The human gut is the largest organ with immune function in our body, responsible for regulating the homeostasis of the intestinal barrier. A diverse, complex and dynamic population of microorganisms, called microbiota, which exert a significant impact on the host during homeostasis and disease, supports this role. In fact, intestinal bacteria maintain immune and metabolic homeostasis, protecting our organism against pathogens. The development of numerous inflammatory disorders and infections has been linked to altered gut bacterial composition or dysbiosis. Multiple factors contribute to the establishment of the human gut microbiota. For instance, diet is considered as one of the many drivers in shaping the gut microbiota across the lifetime. By contrast, alcohol is one of the many factors that disrupt the proper functioning of the gut, leading to a disruption of the intestinal barrier integrity that increases the permeability of the mucosa, with the final result of a disrupted mucosal immunity. This damage to the permeability of the intestinal membrane allows bacteria and their components to enter the blood tissue, reaching other organs such as the liver or the brain. Although chronic heavy drinking has harmful effects on the immune system cells at the systemic level, this review focuses on the effect produced on gut, brain and liver, because of their significance in the link between alcohol consumption, gut microbiota and the immune system.

show abstract

“…As expected, salmon sperm DNA significantly reversed the increased IL‐1β level in serum and the CYP2E1 mRNA level in the present study. It is well known that in human and rat models, long‐term alcohol use increases proinflammatory cytokine levels and induces macrophage activation, which further promotes the gene expression of proinflammatory cytokines (Lee et al, 2021). Kupffer cells from alcohol‐gavaged mice showed an enhanced response to LPS.…”

Section: Discussionmentioning

confidence: 99%

Salmon sperm DNA prevents acute liver injury by regulating alcohol‐induced steatosis and restores chronic hepatosis via alleviating inflammation and apoptosis

Xue

Tian

et al. 2022

Journal of Food Biochemistry

View full text Add to dashboard Cite

Current medications used to treat alcoholic liver injury (ALD) can cause secondary damage to the liver. Therefore, it is important to improve alcoholic liver injury from the perspective of dietary and nutritional supplementation. Nucleic acids, as functional biomolecules, are present in almost all foods, especially in aquatic products, but their edible research has been neglected for a long time. Hence, the effects of a typical aquatic nucleic acid, namely, salmon sperm DNA, in acute, and chronic alcoholic liver injury model of male ICR mice were studied. The results showed that salmon sperm DNA significantly attenuated the accumulation of cholesterol (TC) and triglycerides (TG) in acute alcoholic liver injury, and it was further demonstrated to mainly regulate lipid metabolism by fluorescent quantitative PCR and immunoblotting experiments. In addition, nucleic acid intervention alleviated inflammation and apoptosis in mice with chronic alcoholic liver injury. Practical applications These results suggest that salmon sperm DNA can prevent and ameliorate alcoholic liver injury and can be used as an effective dietary and nutritional supplement for the prevention and treatment of ALD. Moreover, this study provided some new ideas for the development and utilization of large aquatic nucleic acid resources, promoted the comprehensive use of fish processing waste, such as fish sperm, and provided new directions for reducing emissions.

show abstract

PCSK9 and the Gut-Liver-Brain Axis: A Novel Therapeutic Target for Immune Regulation in Alcohol Use Disorder

Cited by 15 publications

References 119 publications

Effects of PCSK9 Targeting: Alleviating Oxidation, Inflammation, and Atherosclerosis

Effects of PCSK9 Targeting: Alleviating Oxidation, Inflammation, and Atherosclerosis

The Immune System through the Lens of Alcohol Intake and Gut Microbiota

Salmon sperm DNA prevents acute liver injury by regulating alcohol‐induced steatosis and restores chronic hepatosis via alleviating inflammation and apoptosis

Contact Info

Product

Resources

About