Characterization of PCSK9 in the Blood and Skin of Psoriasis

Garshick, Michael; Baumer, Yvonne; Dey, Amit; Grattan, Ryan; Ng, Qimin; Teague, Heather; Yu, Zu‐Xi; Chen, Marcus Y; Tawil, Michael; Barrett, Tessa J.; Underberg, James; Fisher, Edward A.; Krueger, James G.; Powell‐Wiley, Tiffany M.; Playford, Martin P.; Mehta, Nehal N.

doi:10.1016/j.jid.2020.05.115

Cited by 29 publications

(18 citation statements)

References 29 publications

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“…On the other hand, high serum levels of PCSK9 have been associated with different vascular diseases such as vasculitis, atherosclerosis, arterial calcification, cerebrovascular, and aortic diseases [ 26 ]. Additionally, various reports have linked PCSK9 with systemic lupus erythematosus [ 27 , 28 ], rheumatoid arthritis [ 29 , 30 ], psoriasis [ 31 , 32 ], systemic sclerosis [ 33 ], and nephrotic syndrome [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Variants of PCSK9 Gene Are Associated with Subclinical Atherosclerosis and Cardiometabolic Parameters in Mexicans. The GEA Project

et al. 2021

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Background: Coronary artery disease (CAD) is a chronic, inflammatory, and complex disease associated with vascular risk factors. Nowadays, the coronary artery calcium (CAC) is a specific marker of the presence and extent of atherosclerosis. Additionally, CAC is a predictor of future coronary events in asymptomatic individuals diagnosed with subclinical atherosclerosis (CAC > 0). In this study, our aim is to evaluate the participation of two polymorphisms of the PCSK9 gene as genetic markers for developing subclinical atherosclerosis and cardiometabolic risk factors in asymptomatic individuals. Methods: We analyzed two PCSK9 polymorphisms (rs2479409 and rs615563) in 394 individuals with subclinical atherosclerosis and 1102 healthy controls using real time- polymerase chain reaction (PCR). Results: Under various inheritance models adjusted for different confounding factors, the rs2479409 polymorphism was associated with an increased risk of developing subclinical atherosclerosis (OR = 1.53, P recessive = 0.041). Both polymorphisms were significantly associated with several cardiometabolic parameters. Conclusions: Our data suggest that rs2479409 polymorphism could be envisaged as a risk marker for subclinical atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Variants of PCSK9 Gene Are Associated with Subclinical Atherosclerosis and Cardiometabolic Parameters in Mexicans. The GEA Project

et al. 2021

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Section: Neutrophils and Blood Transcriptome Signature In Psoriasismentioning

confidence: 99%

“…Recently, the same authors characterized the levels of PCSK9 and cardiovascular risk in the blood and skin of psoriatic patients [ 82 ]. The study, involving two separate human psoriasis cohorts, showed increased levels of PCSK9 in psoriatic patients compared to age-, sex-, and cholesterol-matched controls [ 82 ]. The PCSK9 levels correlated with impaired endothelial vascular health and coronary artery calcium score, suggesting an association between circulating PCSK9 and early, as well as advanced, stages of atherosclerosis in psoriasis.…”

Section: Neutrophils and Blood Transcriptome Signature In Psoriasismentioning

confidence: 99%

Transcriptional Basis of Psoriasis from Large Scale Gene Expression Studies: The Importance of Moving towards a Precision Medicine Approach

Krishnan

Kõks

2022

IJMS

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Transcriptome profiling techniques, such as microarrays and RNA sequencing (RNA-seq), are valuable tools for deciphering the regulatory network underlying psoriasis and have revealed large number of differentially expressed genes in lesional and non-lesional skin. Such approaches provide a more precise measurement of transcript levels and their isoforms than any other methods. Large cohort transcriptomic analyses have greatly improved our understanding of the physiological and molecular mechanisms underlying disease pathogenesis and progression. Here, we mostly review the findings of some important large scale psoriatic transcriptomic studies, and the benefits of such studies in elucidating potential therapeutic targets and biomarkers for psoriasis treatment. We also emphasised the importance of looking into the alternatively spliced RNA isoforms/transcripts in psoriasis, rather than focussing only on the gene-level annotation. The neutrophil and blood transcriptome signature in psoriasis is also briefly reviewed, as it provides the immune status information of patients and is a less invasive platform. The application of precision medicine in current management of psoriasis, by combining transcriptomic data, improves the clinical response outcome in individual patients. Drugs tailored to individual patient’s genetic profile will greatly improve patient outcome and cost savings for the healthcare system.

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“…Moreover, the local expression of PCSK9 is increased in response to local inflammation triggered by agonists of TLR4, LOX-1, or TNFα ( Krahel et al, 2020b ). More importantly, PCSK9 associated with psoriasis appears to be independent of cholesterol metabolism ( Garshick et al, 2020 ).…”

Section: The Role Of Pcsk9 In Other Organsmentioning

confidence: 99%

Coming Back to Physiology: Extra Hepatic Functions of Proprotein Convertase Subtilisin/Kexin Type 9

2020

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Neuronal apoptosis regulated convertase-1 (NARC-1), now mostly known as proprotein convertase subtilisin/kexin type 9 (PCSK9), has received a lot of attention due to the fact that it is a key regulator of the low-density lipoprotein (LDL) receptor (LDL-R) and is therefore involved in hepatic LDL clearance. Within a few years, therapies targeting PCSK9 have reached clinical practice and they offer an additional tool to reduce blood cholesterol concentrations. However, PCSK9 is almost ubiquitously expressed in the body but has less well-understood functions and target proteins in extra hepatic tissues. As such, PCSK9 is involved in the regulation of neuronal survival and protein degradation, it affects the expression of the epithelial sodium channel (ENaC) in the kidney, it interacts with white blood cells and with cells of the vascular wall, and it modifies contractile activity of cardiomyocytes, and contributes to the regulation of cholesterol uptake in the intestine. Moreover, under stress conditions, signals from the kidney and heart can affect hepatic expression and thereby the plasma concentration of PCSK9 which then in turn can affect other target organs. Therefore, there is an intense relationship between the local (autocrine) and systemic (endocrine) effects of PCSK9. Although, PCSK9 has been recognized as a ubiquitously expressed modifier of cellular function and signaling molecules, its physiological role in different organs is not well-understood. The current review summarizes these findings.

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Characterization of PCSK9 in the Blood and Skin of Psoriasis

Cited by 29 publications

References 29 publications

Variants of PCSK9 Gene Are Associated with Subclinical Atherosclerosis and Cardiometabolic Parameters in Mexicans. The GEA Project

Variants of PCSK9 Gene Are Associated with Subclinical Atherosclerosis and Cardiometabolic Parameters in Mexicans. The GEA Project

Transcriptional Basis of Psoriasis from Large Scale Gene Expression Studies: The Importance of Moving towards a Precision Medicine Approach

Coming Back to Physiology: Extra Hepatic Functions of Proprotein Convertase Subtilisin/Kexin Type 9

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