The Emerging Role of PCSK9 Inhibitors in Preventive Cardiology

Pitts, Reynaria; Eckel, Robert H.

doi:10.15420/ecr.2014.9.2.65

Cited by 7 publications

(5 citation statements)

References 65 publications

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“…Then, it forms the LDL-R complex upon binding with the EGF-A domain and reenters into the hepatocytes through the endocytosis. In the intracellular pathway, PCSK9 could bind the endocytosed LDL-R and direct the PCSK9-LDL-R-LDL complex to lysosomes for degradation [ 12 , 13 ], and then, the degradation substances were discharged through the bile excretion which reduced the amount of LDL-R. Therefore, the PCSK9 protein plays an important role in the regulation of LDL and cholesterol metabolism.…”

Section: Biology Of Pcsk9mentioning

confidence: 99%

PCSK9: A Potential Therapeutic Target for Sepsis

Yuan

Sun

et al. 2020

Journal of Immunology Research

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Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is often upregulated in the presence of sepsis and infectious diseases. In sepsis, PCSK9 degraded the low-density lipoprotein cholesterol (LDL) receptors (LDL-R) of the hepatocytes and the very low-density lipoprotein cholesterol receptors (VLDL-R) of the adipocytes, which then subsequently reduced pathogenic lipid uptake and clearance/sequestration. Moreover, it might improve cholesterol accumulation and augment toll-like receptor function in macrophages, which supported inflammatory responses. Accordingly, PCSK9 might show detrimental effects on immune host response and survival in sepsis. However, the exact roles of PCSK9 in the pathogenesis of sepsis are still not well defined. In this review, we summarized the literatures focusing on the roles of PCSK9 in sepsis. Our review provided an additional insight in the role of PCSK9 in sepsis, which might serve as a potential target for the treatment of sepsis.

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Section: Biology Of Pcsk9mentioning

confidence: 99%

PCSK9: A Potential Therapeutic Target for Sepsis

Yuan

Sun

et al. 2020

Journal of Immunology Research

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“…Other potential mechanisms of PCSK-9 inhibition to control LDL-C include gene silencing including antisense oligonucleotide, small interfering RNA (siRNA), peptides that mimic PCSK-9 and small molecule inhibitors of PCSK-9 [11]. A gain or loss of function is also found in PCSK-9 gene mutations [11]. A gain of function of PCSK-9 is due to missense mutations and increases levels/affinity of PCSK-9.…”

Section: Discussionmentioning

confidence: 99%

“…A gain of function of PCSK-9 is due to missense mutations and increases levels/affinity of PCSK-9. A loss of function of PCSK-9 is due to non-sense /missense mutations and decreases levels/affinity of PCSK-9 [11].…”

Section: Discussionmentioning

confidence: 99%

Proprotein convertase subtilisin/Kexin type-9 (PCSK-9) inhibitors induced liver injury - a retrospective analysis

Zafar

Sattar

Ullah

et al. 2020

Journal of Community Hospital Internal Medicine Perspectives

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Background: Proprotein convertase subtilisin/Kexin type 9 (PCSK-9) inhibitors induced liver dysfunction in patients with or without previous liver injury, and this is not well discussed in the previous literature. Methods: A total sample of 202 patients were retrospectively reviewed at the University of Missouri, Kansas City, from the year 2015 to 2018 based on predefined selection criteria. Inclusion criteria involved patients with dyslipidemia, with or without PCSK-9 inhibitors, liver function tests and lipid profile at baseline and at a mean of 6-month follow-up. The variables, including age, gender, and confounding factors like other medications (statin, oral antidiabetic, and antihypertensive) induced, or chronic secondary liver diseases causing liver injury were taken into consideration. Exclusion criteria included patients without dyslipidemia. Results: The mean age of the study population was 64 ± 11 years (63% males and 37% females). The lipid profile including triglyceride and cholesterol levels during 6-month followup visit showed a mean of 184 ± 260 and 163 ± 50 mg/dL as compared to that at baseline of 227 ± 603 and 181 ± 70 mg/dL, respectively. In terms of clinical efficacy, a 6-month follows-up showed a drop in triglyceride and cholesterol levels by 38 and 15 mg/dL, respectively. A liver function test at 6 months in patients taking PCSK-9 inhibitors showed an increase in alanine transaminase (ALT) and aspartate transaminase (AST) by 5.8 mg/dL (p = 0.037) and 6.2 mg/dL (p = 0.008), respectively, from baseline values. Conclusion: PCSK-9 inhibitors should be used cautiously with a follow-up liver function test.

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“…Three PCSK9 monoclonal antibodies included in the present review are: alirocumab (Praluent), evolocumab (Repatha) and bococizumab. The latter was withdrawn from development in 2016 (Bove et al, 2019;Schwartz et al, 2018;Sabatine et al, 2017;Pitts and Eckel, 2014). It should be noted that in the publication by Pitts and Eckel, the PCSK9 inhibitor bococizumab was mistakenly referred to as bocolicumab (Pitts and Eckel, 2014).…”

Section: Pcsk9 Inhibitorsmentioning

confidence: 99%

A short review of proprotein convertase subtilisin/kexin type 9 inhibitors

Rudaynah

2019

Reviews in Cardiovascular Medicine

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Cardiovascular disease is the leading cause of morbidity and mortality globally, as estimated by the World Health Organization, where in 2016, 15.2 million deaths were attributed to ischemic heart disease and stroke. It is therefore essential to try to reduce the incidence of Cardiovascular disease by controlling modifiable risk factors. One such major modifiable risk factor is cholesterol, which influences the pathogenesis and progression of atherosclerosis. Statins are often prescribed to lower blood levels of low density lipoprotein cholesterol, thereby reducing the risk of Cardiovascular disease by approximately 25-35%. However, there is an increasing number of patients (in particular those with intolerance to statin therapy and those with familial hypercholesterolemia) for whom statin therapy alone is not enough to control low density lipoprotein cholesterol. In this review, the regulation of cholesterol metabolism will be discussed with an emphasis on novel cholesterol lowering drugs used in clinical trials. These second-generation drugs, monoclonal antibodies against the low density lipoprotein receptor gene known as proprotein convertase subtilisin/kexin type 9 inhibitors, are expected to be prescribed to patients who are intolerant to statins, as well as in conjunction with statins. Future perspectives of the clinical use of these drugs is also discussed.

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The Emerging Role of PCSK9 Inhibitors in Preventive Cardiology

Cited by 7 publications

References 65 publications

PCSK9: A Potential Therapeutic Target for Sepsis

PCSK9: A Potential Therapeutic Target for Sepsis

Proprotein convertase subtilisin/Kexin type-9 (PCSK-9) inhibitors induced liver injury - a retrospective analysis

A short review of proprotein convertase subtilisin/kexin type 9 inhibitors

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