Effect of Preoperative Administration of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor on Carotid Artery Stenting

Shingai, Yuto; Kimura, Naoto; Takahashi, Kei; Yokosawa, Michiko; Kanoke, Atsushi; Kikuchi, Toshihiro; Sugawara, Takayuki; Tominaga, Teiji

doi:10.1016/j.wneu.2019.10.095

Cited by 6 publications

(6 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a cohort including 28 patients, the lipid content of carotid plaque was reduced by 17% after 6 months of PCSK9 inhibition with alirocumab 25 . Furthermore, Shingai et al concluded that PCSK9 inhibitor may possibly stabilize carotid plaque and reduce perioperative complications of stenting based on a cohort of nine patients 26 . Our study preliminarily determined the potential of plasma PCSK9 as an indicator of unstable carotid plaque (Table 1, Table S1).…”

Section: Discussionmentioning

confidence: 65%

“…25 Furthermore, Shingai et al concluded that PCSK9 inhibitor may possibly stabilize carotid plaque and reduce perioperative complications of stenting based on a cohort of nine patients. 26 Our study preliminarily determined the potential of plasma PCSK9 as an indicator of unstable carotid plaque ( In early-stage atherosclerosis, VSMCs migrate from the media to the intima and proliferate, wrap the necrotic core by secreting extracellular matrix, and inhibiting the rupture of the fibrous cap. 27 However, VSMCs' apoptosis is abnormal in advanced plaques, which weakened fibrous cap and enlarged necrotic cores.…”

Section: Discussionmentioning

confidence: 99%

“… 25 Furthermore, Shingai et al concluded that PCSK9 inhibitor may possibly stabilize carotid plaque and reduce perioperative complications of stenting based on a cohort of nine patients. 26 Our study preliminarily determined the potential of plasma PCSK9 as an indicator of unstable carotid plaque (Table 1 , Table S1 ). Our findings may enrich the evidence for the clinical application of PCSK9‐based diagnostics and prognosis prediction for patients with carotid atherosclerotic stenosis.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

PCSK9 increases vulnerability of carotid plaque by promoting mitochondrial dysfunction and apoptosis of vascular smooth muscle cells

Xu,

Li,

Luo

et al. 2024

CNS Neurosci Ther

View full text Add to dashboard Cite

BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) has been recognized as a novel lipid‐lowing target. Recent clinical studies suggested the value of inhibiting PCSK9 in decreasing the vulnerability of coronary plaques. However, the evidence of PCSK9‐regulated evolution of unstable carotid plaques is unclear, which has limited the use of PCSK9 inhibitor in carotid plaques. This study aimed to determine the effect and molecular mechanisms of PCSK9 on vulnerability of carotid plaques, to provide potential therapeutic targets for stabilizing carotid plaques.MethodsThe expression of PCSK9 in stable and unstable carotid plaques were examined in tissue and plasma. Human aortic vascular smooth muscle cells (VSMCs) and carotid VSMCs were employed to transfect lentivirus for overexpression and knockdown of PCSK9, respectively. Morphological and functional changes of mitochondria were observed by live‐cell imaging. Cell apoptosis was evaluated by propidium iodide staining. RNA‐sequencing and biological examinations were performed to explore and validate the underlying mechanisms. Truncated plasmids were employed to identify the functional domain of PCSK9 in regulation of VSMCs' mitochondrial morphology, function and apoptosis.ResultsClinically, PCSK9 was closely related with vulnerability of human carotid plaques. Increased expression of PCSK9 in human VSMCs was accompanied by higher level of apoptosis. At subcellular level of VSMCs, the morphology of mitochondria was shifted toward the fission state, followed by mitochondrial dysfunction. Inhibition of p38 MAPK activation partially rescued the above morphological and behavioral changes caused by PCSK9. Furthermore, inhibiting of dynamin‐related protein 1 (DRP1) attenuated PCSK9‐related mitochondrial dysfunction and cell apoptosis. The 1‐149aa domain of PCSK9 protein was essential to achieve functional regulation to VSMCs.ConclusionOur findings demonstrated that PCSK9 induced morphology‐related mitochondrial dysfunction and apoptosis of VSMCs, which may be related to increased vulnerability of carotid plaque.

show abstract

Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

“… 25 Furthermore, Shingai et al concluded that PCSK9 inhibitor may possibly stabilize carotid plaque and reduce perioperative complications of stenting based on a cohort of nine patients. 26 Our study preliminarily determined the potential of plasma PCSK9 as an indicator of unstable carotid plaque (Table 1 , Table S1 ). Our findings may enrich the evidence for the clinical application of PCSK9‐based diagnostics and prognosis prediction for patients with carotid atherosclerotic stenosis.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

PCSK9 increases vulnerability of carotid plaque by promoting mitochondrial dysfunction and apoptosis of vascular smooth muscle cells

Xu,

Li,

Luo

et al. 2024

CNS Neurosci Ther

View full text Add to dashboard Cite

show abstract

“…54 Preliminary evidence suggests that preoperative administration of PCSK9 inhibitors stabilize carotid plaques and reduce perioperative complications in patients undergoing CAS. 55 The beneficial effects of PCSK9 inhibitors on carotid plaque composition and regression will be investigated in the on-going CARotid plaqUe StabilizatiOn and regression with evolocumab (CARUSO) study. 56 Drawbacks associated with PCSK9 inhibitor use PCSK9 inhibitors are well-tolerated and safe with only mild sideeffects reported.…”

Section: Drawbacks Associated With Statin Usementioning

confidence: 99%

Benefits and drawbacks of statins and non-statin lipid lowering agents in carotid artery disease

Paraskevas¹,

Gloviczki

Antignani³

et al. 2022

Progress in Cardiovascular Diseases

View full text Add to dashboard Cite

“…Regarding the pivotal role of lipids in atherothrombotic stroke, LDL and modified LDL are potentially important targets. A recent study has reported that PCSK9 administration in combination with statins has efficiently lowered LDLc levels and has reduced the operative complications of carotid stenting probably by stabilizing carotid artery plaque [197]. Other future therapies aiming to reduce the modification of LDL and/or to improve the qualitative properties of LDL and HDL may be very considerably valuable in preventing carotid atherosclerosis progression and complications.…”

Section: Novel Therapiesmentioning

confidence: 99%

Search for Reliable Circulating Biomarkers to Predict Carotid Plaque Vulnerability

Puig

Jiménez‐Xarrié

Camps‐Renom

et al. 2020

IJMS

View full text Add to dashboard Cite

Atherosclerosis is responsible for 20% of ischemic strokes, and the plaques from the internal carotid artery the most frequently involved. Lipoproteins play a key role in carotid atherosclerosis since lipid accumulation contributes to plaque progression and chronic inflammation, both factors leading to plaque vulnerability. Carotid revascularization to prevent future vascular events is reasonable in some patients with high-grade carotid stenosis. However, the degree of stenosis alone is not sufficient to decide upon the best clinical management in some situations. In this context, it is essential to further characterize plaque vulnerability, according to specific characteristics (lipid-rich core, fibrous cap thinning, intraplaque hemorrhage). Although these features can be partly detected by imaging techniques, identifying carotid plaque vulnerability is still challenging. Therefore, the study of circulating biomarkers could provide adjunctive criteria to predict the risk of atherothrombotic stroke. In this regard, several molecules have been found altered, but reliable biomarkers have not been clearly established yet. The current review discusses the concept of vulnerable carotid plaque, and collects existing information about putative circulating biomarkers, being particularly focused on lipid-related and inflammatory molecules.

show abstract

Effect of Preoperative Administration of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor on Carotid Artery Stenting

Cited by 6 publications

References 19 publications

PCSK9 increases vulnerability of carotid plaque by promoting mitochondrial dysfunction and apoptosis of vascular smooth muscle cells

PCSK9 increases vulnerability of carotid plaque by promoting mitochondrial dysfunction and apoptosis of vascular smooth muscle cells

Benefits and drawbacks of statins and non-statin lipid lowering agents in carotid artery disease

Search for Reliable Circulating Biomarkers to Predict Carotid Plaque Vulnerability

Contact Info

Product

Resources

About