Circulating levels of the terminal complement complex are associated with hypercoagulability in patients with stable coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FWF Background and aims Proprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis and can be divided into three subsets. The aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets. Methods We included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14 + CD16++; NCM). Results Mean age was 64 years and 80% of patients were male. Patients on statin treatment (n = 55) showed higher PCSK9-levels (245.4 (206.0-305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3-275.4) ng/mL; p = 0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R = 0.29; p = 0.04), while NCM showed an inverse correlation with PCSK9 levels (R=-0.33; p = 0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK-9 below the median (83.5 IQR 79.2-86.7 vs. 80.4, IQR 76.5-85.2%; p = 0.05). Conversely, PCSK9 levels >median were associated with a significantly lower proportion of NCM as compared to those with PCSK9 <median (10.2, IQR 7.3-14.6 vs. 14.3, IQR 10.9-18.7%; p = 0.02). In contrast, IM showed no association with PCSK-9 levels. Conclusions We hereby provide a novel link between PCSK9 regulation, innate immunity and atherosclerotic disease in statin-treated patients.

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Circulating levels of TNF-like cytokine 1A correlate with reflected waves and atherosclerosis extent and may predict cardiac death in patients with stable coronary artery disease

Cytokine ◽

10.1016/j.cyto.2014.12.016 ◽

2015 ◽

Vol 72 (1) ◽

pp. 102-104 ◽

Cited By ~ 3

Author(s):

Kimon Stamatelopoulos ◽

Stylianos Georgiou ◽

Ioannis Kanakakis ◽

Christos Papamichael ◽

Nikolaos Oikonomidis ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiac Death ◽

Stable Coronary Artery Disease ◽

Reflected Waves ◽

Artery Disease ◽

Circulating Levels

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Genetic variation, gene-expression and circulating levels of matrix metalloproteinase-9 in patients with stable coronary artery disease

Clinica Chimica Acta ◽

10.1016/j.cca.2011.09.004 ◽

2012 ◽

Vol 413 (1-2) ◽

pp. 113-120 ◽

Cited By ~ 15

Author(s):

Trine B. Opstad ◽

Alf-Aage R. Pettersen ◽

Thomas W. Weiss ◽

Sissel Åkra ◽

Reidun Øvstebø ◽

...

Keyword(s):

Gene Expression ◽

Coronary Artery Disease ◽

Genetic Variation ◽

Coronary Artery ◽

Matrix Metalloproteinase ◽

Stable Coronary Artery Disease ◽

Matrix Metalloproteinase 9 ◽

Artery Disease ◽

Circulating Levels ◽

Metalloproteinase 9

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Cyclophilin A and matrix metalloproteinase-9: Their relationship, association with, and diagnostic relevance in stable coronary artery disease

Vascular ◽

10.1177/1708538119879589 ◽

2019 ◽

Vol 28 (2) ◽

pp. 212-221 ◽

Cited By ~ 1

Author(s):

Hala F Ebrahim ◽

Fatma F Abdel Hamid ◽

Mohamed A Haykal ◽

Ahmed F Soliman

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Matrix Metalloproteinase ◽

Stable Coronary Artery Disease ◽

Cyclophilin A ◽

Matrix Metalloproteinase 9 ◽

Artery Disease ◽

Circulating Levels ◽

Metalloproteinase 9 ◽

Normal Controls

Objectives Data about the circulating levels of cyclophilin A and matrix metalloproteinase-9 in stable coronary artery disease are contradictory. Moreover, their relationship in this disease is not established yet. Thus, this study was designed to assess the relationship between the circulating levels of cyclophilin A and matrix metalloproteinase-9 in coronary artery disease patients with and without type 2 diabetes mellitus (T2DM). Methods Serum levels of cyclophilin A, matrix metalloproteinase-9, and high sensitive C-reactive protein (hsCRP) along with fasting blood glucose, glycated hemoglobin, serum lipids, and the anthropometric parameters were measured in 120 participants who were divided equally into four groups (i) normal controls, (ii) T2DM patients, (iii) stable coronary artery disease patients with T2DM, and (iv) stable coronary artery disease patients without T2DM. Results Levels of cyclophilin A and matrix metalloproteinase-9 were significantly elevated in sera of coronary artery disease patients with and without T2DM compared to normal controls and T2DM patients. In multiple linear regression models, only cyclophilin A was observed in the final model where it explained the 24.9% variability of matrix metalloproteinase-9. Additionally, high circulating levels of cyclophilin A and matrix metalloproteinase-9 were associated with an increased risk of developing stable coronary artery disease. Finally, the diagnostic efficacy of cyclophilin A and matrix metalloproteinase-9 to discriminate stable coronary artery disease patients with and without T2DM from subjects without coronary artery disease was found to be higher than that of hsCRP. Conclusion Serum level of cyclophilin A might be a determinant factor of matrix metalloproteinase-9 level; both may contribute to the pathogenesis of stable coronary artery disease and they appear to be valuable diagnostic biomarkers of stable coronary artery disease with and without T2DM.

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Home-based exercise in stable coronary artery disease lowers circulating levels of angiogenic cytokines

European Heart Journal ◽

10.1093/eurheartj/eht309.p3393 ◽

2013 ◽

Vol 34 (suppl 1) ◽

pp. P3393-P3393

Author(s):

S. Duttaroy ◽

J. Nilsson ◽

O. Hammarsten ◽

B. Wennerblom ◽

M. Borjesson

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Stable Coronary Artery Disease ◽

Home Based ◽

Artery Disease ◽

Circulating Levels ◽

Angiogenic Cytokines

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Abstract 15930: Circulating Levels of Proprotein Convertase Subtilisin/kexin Type 9 (pcsk9) are Associated With Monocyte Subsets in Patients With Stable Coronary Artery Disease

Circulation ◽

10.1161/circ.142.suppl_3.15930 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Konstantin Krychtiuk ◽

Max Lenz ◽

Philipp Hohensinner ◽

Klaus Distelmaier ◽

Lore Schrutka ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Stable Coronary Artery Disease ◽

Statin Treatment ◽

Lipid Lowering ◽

Monocyte Subsets ◽

Proprotein Convertase ◽

Artery Disease ◽

Circulating Levels ◽

Classical Monocytes

Introduction: Proprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis. Circulating monocytes can be divided into three subsets. The aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets. Methods: We included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14+CD16++; NCM). Results: Mean age was 64 years and 80% of patients were male. Patients on statin treatment (n=55) showed higher PCSK9-levels (245.4 (206.0-305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3-275.4) ng/mL; p=0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R=0.29; p=0.04), while NCM showed an inverse correlation with PCSK9 levels (R=-0.33; p=0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK-9 below the median (83.5 IQR 79.2-86.7 vs. 80.4, IQR 76.5-85.2%; p=0.05). Conversely, patients with PCSK9 levels >median were associated with a significantly lower proportion of NCM as compared to those with PCSK9 <median (10.2, IQR 7.3-14.6 vs. 14.3, IQR 10.9-18.7%; p=0.02). In contrast, IM showed no association with PCSK-9 levels. Conclusions: We hereby provide a novel link between PCSK9 regulation, innate immunity and atherosclerotic disease in statin-treated patients.

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