Proprotein Convertase Subtilisin/Kexin Type 9 Is Associated with Degenerating Adipocytes in Abdominal Aortic Aneurysm

Tanaka, Hiroki; Inuzuka, Kazunori; Iida, Yasunori; Shimizu, Hideyuki; Unno, Naoki; Urano, Tetsumei

doi:10.5650/jos.ess18131

Cited by 9 publications

(11 citation statements)

References 16 publications

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“…It was proposed that decreased PCSK9 in aortic adventitia might upregulate adipocytokine expression in hypertrophic adipocytes through CD36 degradation, thereby contributing to AAA formation. Taken together, these findings suggest that PCSK9 may promote the development of atherosclerosis and upregulate extracellular matrix degradation and adipocytokine expression, thereby contributing to the AAA formation [10]. As shown in the literature, the role of PCSK 9 in the formation of AAA was demonstrated, and thereby it can also be incriminated in our patient, as well.…”

Section: Discussionsupporting

confidence: 82%

“…Basically, even the ESC guidelines for dyslipidemia management show that, under exclusive statin treatment, the LDL reduction rate is at most 50%. By adding a PCSK9 inhibitor, it increases to at least 75%, implicitly decreasing the risk of CV events [10]. We have preferred the therapeutic combination of atorvastatin 20 mg/day (low dose due to significant hepatic cytolysis at admission) + PCSK9 inhibitor 75 mg SC once every 2 weeks.…”

Section: Discussionmentioning

confidence: 99%

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Young Age Onset Multivascular Pathology in a Patient with Severe Dyslipidemia: an Incidental Case or a Particular Type of Familial Hypercholesterolemia?

Miftode

Haba

Ursaru

et al. 2022

Romanian Journal of Cardiology

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Familial hypercholesterolemia (FH) is a genetic disorder that affects about 1 in 250 people and increases the likelihood of having coronary heart disease at a younger age. We present the case of a 55-year-old patient, known with inferior and anterior myocardial infarction treated by percutaneous coronary intervention and coronary artery bypass grafts, Leriche syndrome, aortic abdominal aneurysm, and bilateral renal stents—pathologies with onset at a young age—who was admitted for fast-paced palpitations, accompanied by increased fatigue. The coronarography did not reveal any acute lesions, but the presence of ventricular tachycardia at admission required the implantation of a cardiac defibrillator. Since the patient presented with early onset severe systemic atherosclerosis, with a lipid profile dominated by hypo-HDL, doubled by an apolipoprotein A1 deficiency, we considered the diagnosis of familial hypercholesterolemia. Due to the high-risk profile, the association between a statin and a PCSK9 inhibitor was initiated at discharge. At the 1-month follow-up control, a significant reduction of LDL-C has been achieved, with a simultaneous increase of HDL-C serum levels.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Young Age Onset Multivascular Pathology in a Patient with Severe Dyslipidemia: an Incidental Case or a Particular Type of Familial Hypercholesterolemia?

Miftode

Haba

Ursaru

et al. 2022

Romanian Journal of Cardiology

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“…This study indicated that other LDLR‐independent mechanisms might be involved in PCSK9‐induced AAA. Interestingly, the histological examination revealed a significant increase in PCSK9 expression in degenerative media and a decreased PCSK9 and increased CD36 expression in the adventitia region of human aneurysmal samples (Tanaka et al, 2018). It was reported that increased CD36 expression contributes to the accumulation of hypertrophic adipocytes in the aortic adventitia, and hypertrophic adipocytes secrete excessive adipocytokines that are associated with AAA pathogenesis (Doderer et al, 2018; Kugo et al, 2016; Tanaka et al, 2015).…”

Section: Pcsk9 and Vascular Diseasementioning

confidence: 99%

“…It was reported that increased CD36 expression contributes to the accumulation of hypertrophic adipocytes in the aortic adventitia, and hypertrophic adipocytes secrete excessive adipocytokines that are associated with AAA pathogenesis (Doderer et al, 2018; Kugo et al, 2016; Tanaka et al, 2015). Therefore, it was proposed that decreased PCSK9 in aortic adventitia might upregulate adipocytokine expression in hypertrophic adipocytes through CD36 degradation, thereby contributing to AAA formation (Figure 4; Tanaka et al, 2018). Taken together, these findings suggest that PCSK9 may enhance the apoptosis and dedifferentiation of VSMCs, promote the development of atherosclerosis, and upregulate extracellular matrix degradation and adipocytokine expression, thereby contributing to the AAA formation.…”

Section: Pcsk9 and Vascular Diseasementioning

confidence: 99%

Physiology and role of PCSK9 in vascular disease: Potential impact of localized PCSK9 in vascular wall

Guo

Yan

Gui

et al. 2020

Journal Cellular Physiology

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Proprotein convertase subtilisin/kexin type‐9 (PCSK9), a member of the proprotein convertase family, is an important drug target because of its crucial role in lipid metabolism. Emerging evidence suggests a direct role of localized PCSK9 in the pathogenesis of vascular diseases. With this in our consideration, we reviewed PCSK9 physiology with respect to recent development and major studies (clinical and experimental) on PCSK9 functionality in vascular disease. PCSK9 upregulates low‐density lipoprotein (LDL)‐cholesterol levels by binding to the LDL‐receptor (LDLR) and facilitating its lysosomal degradation. PCSK9 gain‐of‐function mutations have been confirmed as a novel genetic mechanism for familial hypercholesterolemia. Elevated serum PCSK9 levels in patients with vascular diseases may contribute to coronary artery disease, atherosclerosis, cerebrovascular diseases, vasculitis, aortic diseases, and arterial aging pathogenesis. Experimental models of atherosclerosis, arterial aneurysm, and coronary or carotid artery ligation also support PCSK9 contribution to inflammatory response and disease progression, through LDLR‐dependent or ‐independent mechanisms. More recently, several clinical trials have confirmed that anti‐PCSK9 monoclonal antibodies can reduce systemic LDL levels, total nonfatal cardiovascular events, and all‐cause mortality. Interaction of PCSK9 with other receptor proteins (LDLR‐related proteins, cluster of differentiation family members, epithelial Na+ channels, and sortilin) may underlie its roles in vascular disease. Improved understanding of PCSK9 roles and molecular mechanisms in various vascular diseases will facilitate advances in lipid‐lowering therapy and disease prevention.

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“…The association between serum PCSK9 concentrations and the progression of abdominal aortic aneurysm also presented a clinical translation since the increased PCSK9 concentrations could reduce the hepatic LDL receptor (LDLR), resultantly causing the higher LDL-C and further promoted the progression of hyperlipidemia [46,47]. Furthermore, the inflammatory response and dyslipidemia were correlated due to the risk of dyslipidemic related cardio-metabolic diseases could be also induced by lowgrade inflammatory response via the stimulation of the NLRP3 inflammasome and other pro-inflammatory signaling pathways [48,49].…”

Section: Mechanic Linkage Between the Risk Of Dyslipidemia With Bavmentioning

confidence: 99%

Molecular Linkage under the Bicuspid Aortic Valve with Dyslipidemia

Wu¹,

Yao²,

Hj³

et al. 2023

Front. Biosci. (Landmark Ed)

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Dyslipidemia is correlated with diverse cardiovascular problems, such as obesity, hypertension, and atherosclerosis, which are summarized as metabolic syndrome. Bicuspid aortic valve (BAV), as one of the congenital heart defects, is shown to influence approximately 2.2% of the general population worldwide, inducing the severe pathological development of aortic valve stenosis (AVS) or aortic valve regurgitation (AVR), and also to aortic dilatation. Notably, emerging evidence showed that BAV was correlated with not only the aortic valve and wall diseases but also the dyslipidemic related cardiovascular disorders. Recent results also proposed that multiple potential molecular mechanisms inducing the progression of dyslipidemia played important roles in BAV and the progression of AVS. Several altered serum biomarkers under dyslipidemic condition, including higher low-density lipoprotein cholesterol (LDL-C), higher lipoprotein (a) [Lp(a)], lower high-density lipoprotein cholesterol (HDL-C), and different pro-inflammatory signaling pathways, have proposed to embrace a vital function in the development of BAV correlated cardiovascular diseases. In this review, different molecular mechanisms which embrace an important role in personalized prognosis in the subjects with BAV was summarized. The illustration of those mechanisms might facilitate an accurate follow-up for patients with BAV and give new pharmacological strategies to improve development of dyslipidemia and BAV.

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Proprotein Convertase Subtilisin/Kexin Type 9 Is Associated with Degenerating Adipocytes in Abdominal Aortic Aneurysm

Cited by 9 publications

References 16 publications

Young Age Onset Multivascular Pathology in a Patient with Severe Dyslipidemia: an Incidental Case or a Particular Type of Familial Hypercholesterolemia?

Young Age Onset Multivascular Pathology in a Patient with Severe Dyslipidemia: an Incidental Case or a Particular Type of Familial Hypercholesterolemia?

Physiology and role of PCSK9 in vascular disease: Potential impact of localized PCSK9 in vascular wall

Molecular Linkage under the Bicuspid Aortic Valve with Dyslipidemia

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