PCSK9 and triglyceride-rich lipoprotein metabolism

Druce, Irena; Abujrad, Hussein; Ooi, Teik Chye

doi:10.7555/jbr.29.20150052

Cited by 28 publications

(7 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its function in these tissues may vary, indicating cell and tissue-specific roles. PCSK9 also affects triglyceride-rich lipoproteins, such as very VLDL and chylomicrons 19 . It can influence the production and secretion of VLDL and modulate the metabolism of intestinal chylomicrons, though its impact on plasma triglyceride levels is relatively modest compared to its effect on LDL-C. PCSK9 has garnered significant interest in its role in regulating lipoprotein(a) (Lp(a)), a lipoprotein-associated with an increased risk of CVD 20 .…”

Section: Methodsmentioning

confidence: 99%

Role of PCSK9 inhibition during the inflammatory stage of SARS-COV-2: an updated review

Arsh,

Manoj Kumar,

Simran

et al. 2024

Annals of Medicine &Amp; Surgery

View full text Add to dashboard Cite

The potential role of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) inhibition in the management of COVID-19 and other medical conditions has emerged as an intriguing area of research. PCSK9 is primarily known for its impact on cholesterol metabolism, but recent studies have unveiled its involvement in various physiological processes, including inflammation, immune regulation, and thrombosis. In this abstract, we review the rationale and potential implications of PCSK9 inhibition during the inflammatory stage of SARS-CoV-2 infection. Severe cases of COVID-19 are characterized by an uncontrolled inflammatory response, often referred to as the cytokine storm, which can lead to widespread tissue damage and organ failure. Preclinical studies suggest that PCSK9 inhibition could dampen this inflammatory cascade by reducing the production of pro-inflammatory cytokines. Additionally, PCSK9 inhibition may protect against acute respiratory distress syndrome (ARDS) through its effects on lung injury and inflammation. COVID-19 has been linked to an increased risk of cardiovascular complications, especially in patients with pre-existing cardiovascular conditions or dyslipidemia. PCSK9 inhibitors are known for their ability to lower LDL cholesterol levels by enhancing the recycling of LDL receptors in the liver. By reducing LDL cholesterol, PCSK9 inhibition might protect blood vessels from further damage and lower the risk of atherosclerotic plaque formation. Moreover, PCSK9 inhibitors have shown potential antithrombotic effects in preclinical studies, making them a potential avenue to mitigate the increased risk of coagulation disorders and thrombotic events observed in COVID-19. While the potential implications of PCSK9 inhibition are promising, safety considerations and possible risks need careful evaluation. Hypocholesterolemia, drug interactions, and long-term safety are some of the key concerns that should be addressed. Clinical trials are needed to establish the efficacy and safety of PCSK9 inhibitors in COVID-19 patients and to determine the optimal timing and dosing for treatment. Future research opportunities encompass investigating the immune response, evaluating long-term safety, exploring combination therapy possibilities, and advancing personalized medicine approaches. Collaborative efforts from researchers, clinicians, and policymakers are essential to fully harness the therapeutic potential of PCSK9 inhibition and translate these findings into meaningful clinical outcomes.

show abstract

Section: Methodsmentioning

confidence: 99%

Role of PCSK9 inhibition during the inflammatory stage of SARS-COV-2: an updated review

Arsh,

Manoj Kumar,

Simran

et al. 2024

Annals of Medicine &Amp; Surgery

View full text Add to dashboard Cite

show abstract

“…This tissue is the main storage site of triglycerides (TG). Several lines of evidence suggest that PCSK9 influences the metabolism TGrich lipoproteins (Druce et al 2015). Genetic ablation of the Pcsk9 gene in mice resulted in increased visceral adiposity due to elevated expression of the receptor for TG-rich very lowdensity lipoprotein (VLDLR) on the cell surface of adipocytes (Roubtsova et al 2011;Baragetti et al 2017).…”

Section: Local Versus Systemic Effect On Extrahepatic Tissuesmentioning

confidence: 99%

The biological relevance of PCSK9: when less is better…

Mbikay

Chrétien

2022

Biochem. Cell Biol.

View full text Add to dashboard Cite

Proprotein Convertase Subtilisin/Kexin-type 9 (PCSK9) is a circulating negative regulator of hepatic low-density lipoprotein receptor (LDLR) which clears cholesterol from blood. Gain-of-function genetic mutations which amplify PCSK9 activity have been found to cause potentially lethal familial hypercholesterolemia. Inversely, reduction of its activity through loss-of-function genetics or with pharmaceuticals was shown to increase hepatic LDLR, to lower blood cholesterol, and to protect against cardiovascular diseases. New epidemiological and experimental evidence suggests that this reduction could also attenuate inflammation, reinforce cancer immunity, provide resistance to infections, and protect against liver pathologies. In this review, we question the relevance of this protein under normal physiology. We propose that PCSK9 is an important, but non-essential, modulator of cholesterol metabolism and immunity, and that its pathogenicity results from its chronic overexpression.

show abstract

“…Patients with T1HLP generally present low LDL-C levels and HDL-C levels besides high TG levels (Fojo and Brewer, Frontiers in Genetics frontiersin.org 1992; Blom et al, 2018;O'Dea et al, 2019). Moreover, many studies have reported a potential correlation between plasma PCSK9 levels and LDL-C, but also triglycerides-rich lipoproteins and investigations linking these actors are being conducted (Lakoski et al, 2009;Druce et al, 2015;Norata et al, 2016;Baragetti et al, 2018;Warden et al, 2020). For these reasons, we measured plasma PCSK9 levels in the recruited members of the family.…”

Section: Pcsk9 Measurementsmentioning

confidence: 99%

“…Many studies have reported a potential correlation between plasma PCSK9 levels and LDL-C, but also TG, VLDL-C, and intermediate-density lipoprotein cholesterol (IDL-C). Investigations linking these actors of the lipid pathway are being conducted (Lakoski et al, 2009;Druce et al, 2015;Norata et al, 2016;Baragetti et al, 2018;Warden et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Low circulating PCSK9 levels in LPL homozygous children with chylomicronemia syndrome in a syrian refugee family in Lebanon

et al. 2022

View full text Add to dashboard Cite

Familial chylomicronemia syndrome is a rare autosomal recessive disorder of lipoprotein metabolism characterized by the presence of chylomicrons in fasting plasma and an important increase in plasma triglycerides (TG) levels that can exceed 22.58 mmol/l. The disease is associated with recurrent episodes of abdominal pain and pancreatitis, eruptive cutaneous xanthomatosis, lipemia retinalis, and hepatosplenomegaly. A consanguineous Syrian family who migrated to Lebanon was referred to our laboratory after perceiving familial chylomicronemia syndrome in two children. The LPL and PCSK9 genes were sequenced and plasma PCSK9 levels were measured. Sanger sequencing of the LPL gene revealed the presence of the p.(Val227Phe) pathogenic variant in exon 5 at the homozygous state in the two affected children, and at the heterozygous state in the other recruited family members. Interestingly, PCSK9 levels in homozygous carriers of the p.(Val227Phe) were ≈50% lower than those in heterozygous carriers of the variant (p-value = 0.13) and ranged between the 5th and the 7.5th percentile of PCSK9 levels in a sample of Lebanese children of approximately the same age group. Moreover, this is the first reported case of individuals carrying simultaneously an LPL pathogenic variant and PCSK9 variants, the L10 and L11 leucine insertion, which can lower and raise low-density lipoprotein cholesterol (LDL-C) levels respectively. TG levels fluctuated concomitantly between the two children, were especially high following the migration from a country to another, and were reduced under a low-fat diet. This case is crucial to raise public awareness on the risks of consanguineous marriages to decrease the emergence of inherited autosomal recessive diseases. It also highlights the importance of the early diagnosis and management of these diseases to prevent serious complications, such as recurrent pancreatitis in the case of familial hyperchylomicronemia.

show abstract

PCSK9 and triglyceride-rich lipoprotein metabolism

Cited by 28 publications

References 74 publications

Role of PCSK9 inhibition during the inflammatory stage of SARS-COV-2: an updated review

Role of PCSK9 inhibition during the inflammatory stage of SARS-COV-2: an updated review

The biological relevance of PCSK9: when less is better…

Low circulating PCSK9 levels in LPL homozygous children with chylomicronemia syndrome in a syrian refugee family in Lebanon

Contact Info

Product

Resources

About