Non-Lipid Effects of PCSK9 Monoclonal Antibodies on Vessel Wall

Ugovšek, Sabina; Šebeštjen, Miran

doi:10.3390/jcm11133625

Cited by 10 publications

(4 citation statements)

References 91 publications

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“…Drugs commonly used to reduce high cholesterol levels in dysmetabolic patients, such as statins, have also been largely demonstrated to exert vascular protective effects restoring endothelial NO production, increasing the expression of tissue-type plasminogen activator (t-PA) and attenuating P-selectin expression and leukocyte adherence [ 72 ]. Moreover, PCSK9 monoclonal antibodies have been shown to improve endothelial function, since PCSK9 inhibitors may attenuate the proinflammatory activation of endothelial cells, increase circulating EPCs and promote vascular repair independently from LDL cholesterol regulation [ 73 ].…”

Section: Cardiometabolic Drugs and Endothelial Functionmentioning

confidence: 99%

New Insights into Endothelial Dysfunction in Cardiometabolic Diseases: Potential Mechanisms and Clinical Implications

Gallo,

Savoia

2024

IJMS

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The endothelium is a monocellular layer covering the inner surface of blood vessels. It maintains vascular homeostasis regulating vascular tone and permeability and exerts anti-inflammatory, antioxidant, anti-proliferative, and anti-thrombotic functions. When the endothelium is exposed to detrimental stimuli including hyperglycemia, hyperlipidemia, and neurohormonal imbalance, different biological pathways are activated leading to oxidative stress, endothelial dysfunction, increased secretion of adipokines, cytokines, endothelin-1, and fibroblast growth factor, and reduced nitric oxide production, leading eventually to a loss of integrity. Endothelial dysfunction has emerged as a hallmark of dysmetabolic vascular impairment and contributes to detrimental effects on cardiac metabolism and diastolic dysfunction, and to the development of cardiovascular diseases including heart failure. Different biomarkers of endothelial dysfunction have been proposed to predict cardiovascular diseases in order to identify microvascular and macrovascular damage and the development of atherosclerosis, particularly in metabolic disorders. Endothelial dysfunction also plays an important role in the development of severe COVID-19 and cardiovascular complications in dysmetabolic patients after SARS-CoV-2 infection. In this review, we will discuss the biological mechanisms involved in endothelial dysregulation in the context of cardiometabolic diseases as well as the available and promising biomarkers of endothelial dysfunction in clinical practice.

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Section: Cardiometabolic Drugs and Endothelial Functionmentioning

confidence: 99%

New Insights into Endothelial Dysfunction in Cardiometabolic Diseases: Potential Mechanisms and Clinical Implications

Gallo,

Savoia

2024

IJMS

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“…release and aggregation (40)(41)(42). Early PCSK9 inhibitor treatment can potentially inhibit PCSK9-related inflammatory effects in patients with ACS.…”

Section: Lipid-lowering Effect Of Pcsk9 Inhibitors and Early Implemen...mentioning

confidence: 99%

PCSK9 inhibitors for acute coronary syndrome: the era of early implementation

Chen

2023

Front. Cardiovasc. Med.

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a new cholesterol-lowering strategy, can decrease low-density lipoprotein cholesterol (LDL-C) levels by inhibiting PCSK9 and reducing the degradation of LDL receptors; thus, they are impacting the management of dyslipidemia to the prevention of cardiovascular events. Recent guidelines recommend PCSK9 inhibitors for patients who fail to achieve target lipids after ezetimibe/statin therapy. As PCSK9 inhibitors have been demonstrated to significantly and safely reduce LDL-C, discussions have begun to explore its optimal timing in coronary artery disease, especially in subjects with acute coronary syndrome (ACS). Also, their additional benefits, such as anti-inflammatory effects, plaque regression effects, and cardiovascular event prevention, have become the focus of recent research. Several studies, including EPIC-STEMI, suggest the lipid-lowering effects of early PCSK9 inhibitors in ACS patients, while some studies such as PACMAN-AMI suggest that early PCSK9 inhibitors can decelerate plaque progression and reduce short-term risks of cardiovascular events. Thus, PCSK9 inhibitors are entering the era of early implementation. In this review, we are committed to summarizing the multidimensional benefits of early implementation of PCSK9 inhibitors in ACS.

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“…The status of PCSK9i which possess robust lipid-lowering properties is progressively growing within the most recent clinical guidelines for ACS ( 8 ). Numerous studies have elucidated that PCSK9 inhibitors possess potential broader physiological functions, beyond their established role in lipid level regulation ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

PCSK9 inhibitors ameliorate arterial stiffness in ACS patients: evidences from Mendelian randomization, a retrospective study and basic experiments

Xu,

Wang,

Wang

et al. 2024

Front. Med.

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BackgroundCurrent evidences suggest that Proprotein Convertase Subtilisin/kexin Type 9 inhibitors (PCSK9i) exhibit a protective influence on acute coronary syndrome (ACS). Nevertheless, further investigation is required to comprehend the impact and mechanisms of these pharmaceutical agents on inflammatory factors and arterial stiffness (AS) in patients with ACS. Consequently, the objective of this study is to ascertain the influence of PCSK9i on arterial stiffness in ACS patients and elucidate the underlying mechanisms behind their actions.MethodsThis study employed Mendelian randomization (MR) analysis to examine the association between genetic prediction of PCSK9 inhibition and arterial stiffness. Data of 71 patients with ACS were retrospectively collected, including PCSK9i group (n = 36, PCSK9 inhibitors combined with statins) and control group (n = 35, statins only). Blood lipid levels, inflammatory markers and pulse wave velocity (PWV) data were collected before treatment and at 1 and 6 months after treatment for analysis. Additionally, cell experiments were conducted to investigate the impact of PCSK9i on osteogenesis of vascular smooth muscle cells (VSMCs), utilizing western blot (WB), enzyme-linked immunosorbent assay (ELISA), and calcification index measurements.ResultsThe results of the MR analysis suggest that genetic prediction of PCSK9 inhibition has potential to reduce the PWV. Following treatment of statins combined with PCSK9 inhibitors for 1 and 6 months, the PCSK9i group exhibited significantly lower levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen (FIB) and procalcitonin (PCT) compared to the control group (p < 0.05). Additionally, PWV in the PCSK9i group demonstrated significant reduction after 6 months of treatment and was found to be associated with the circulating CRP level. In cell experiments, PCSK9i pretreatment ameliorated osteogenesis of VSMCs through reducing the deposition of calcium ions, alkaline phosphatase (ALP) activity, and expression of runt-related transcription factor 2 (RUNX2).ConclusionPCSK9i have potential to enhance arterial stiffness in ACS patients. Specifically, at the clinical level, this impact may be attributed to alterations in circulating CRP levels. At the cellular level, it is associated with the signaling pathway linked to RUNX2.

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Non-Lipid Effects of PCSK9 Monoclonal Antibodies on Vessel Wall

Cited by 10 publications

References 91 publications

New Insights into Endothelial Dysfunction in Cardiometabolic Diseases: Potential Mechanisms and Clinical Implications

New Insights into Endothelial Dysfunction in Cardiometabolic Diseases: Potential Mechanisms and Clinical Implications

PCSK9 inhibitors for acute coronary syndrome: the era of early implementation

PCSK9 inhibitors ameliorate arterial stiffness in ACS patients: evidences from Mendelian randomization, a retrospective study and basic experiments

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