LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 LEVELS ARE ASSOCIATED WITH ENDOTHELIAL FUNCTION AND ARTERIAL STIFFNESS IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE

Abstract Background Lipoprotein-associated Phospholipase A2 (Lp-PLA2), has inflammatory and atherogenic actions in the vascular wall. We investigate the impact of high Lp-PLA2 levels on endothelial function and arterial stiffness on patients with coronary artery disease (CAD). Methods We enrolled 374 consecutive patients with stable CAD (mean age 61±11 years). Endothelial function was evaluated by flow-mediated dilation (FMD) and reflected waves with augmentation index (AIx) of the central aortic pressure. Serum levels of Lp-PLA2 were measured with ELISA. Results In the studied population the median values of Lp-PLA2 levels was 125 (96–152) μg/L. There was no difference between subjects with Lp-PLA2 levels above and below 125μg/L concerning classical risk factors for CAD. Importantly, subjects with Lp-PLA2 values ≥125μg/L had significantly impaired FMD (4.44±2.19% vs. 4.89±2.07%, p=0.04) and AIx values (25.21±8.70% vs. 23.06±9.47%, p=0.03), compared to participants with lower Lp-PLA2 serum levels. A linear regression analysis revealed that Lp-PLA2 ≥125μg/L negatively relates to impaired FMD [b=−0.54 (95% CI: −1.05 to −0.02), p=0.04] and AIx values [b=2.14 (95% CI: 0.18–4.01), p=0.03] independently of cofounders. Conclusions Elevated Lp-PLA2 relates to endothelial dysfunction and arterial stiffness in CAD patients. These findings highlight the significant role of Lp-PlA2 in the process of atherosclerosis. Funding Acknowledgement Type of funding source: None

Download Full-text

Coronary Artery Disease and Endothelial Dysfunction: Novel Diagnostic and Therapeutic Approaches

Current Medicinal Chemistry ◽

10.2174/0929867326666190830103219 ◽

2020 ◽

Vol 27 (7) ◽

pp. 1052-1080 ◽

Cited By ~ 2

Author(s):

Evangelos Oikonomou ◽

Gerasimos Siasos ◽

Vasiliki Tsigkou ◽

Evanthia Bletsa ◽

Maria-Evi Panoilia ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Stable Coronary Artery Disease ◽

Therapeutic Interventions ◽

Therapeutic Approaches ◽

Cardiovascular Prognosis ◽

Ultrasound Evaluation ◽

Artery Disease

Coronary artery disease is the leading cause of morbidity and mortality worldwide. The most common pathophysiologic substrate is atherosclerosis which is an inflammatory procedure that starts at childhood and develops throughout life. Endothelial dysfunction is associated with the initiation and progression of atherosclerosis and is characterized by the impaired production of nitric oxide. In general, endothelial dysfunction is linked to poor cardiovascular prognosis and different methods, both invasive and non-invasive, have been developed for its evaluation. Ultrasound evaluation of flow mediated dilatation of the branchial artery is the most commonly used method to assessed endothelial function while intracoronary administration of vasoactive agents may be also be used to test directly endothelial properties of the coronary vasculature. Endothelial dysfunction has also been the subject of therapeutic interventions. This review article summarizes the knowledge about evaluation of endothelial function in acute coronary syndromes and stable coronary artery disease and demonstrates the current therapeutic approaches against endothelial dysfunction.

Download Full-text

Influence of phospholipase A2 and paraoxonase activity on endothelial function changes in various forms of coronary artery disease

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.058 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

VI Maslovskyi ◽

IA Mezhiievska ◽

YV Maslovskyi

Keyword(s):

Coronary Artery Disease ◽

Blood Flow ◽

Coronary Artery ◽

Endothelial Function ◽

Phospholipase A2 ◽

Brachial Artery ◽

Vascular Disorders ◽

Paraoxonase Activity ◽

Artery Disease ◽

Phospholipase A2 Activity

Abstract Funding Acknowledgements Type of funding sources: None. High phospholipase A2 activity is associated with atherosclerotic disorders of the arteries, while paraoxonase activity decreases with increasing atherogenic plasma activity. The purpose is to study the relationship between the combined effect of phospholipase A2 and paraoxonase activity on vascular endothelial dysfunction in various forms of coronary artery disease. We examined 152 men 52.5 ± 0.8 years, including 53 - STEMI, 32 - NSTEMI, 67 - chronic chronic coronary syndromes (CCS). Methods. All patients were examined for endothelial function of the brachial artery with a test for reactive hyperemia and vasodilation with exogenous NO, as well as determination of phospholipase A2 activity and plasma paraoxonase activity. All studiies conform to the principles of the Declaration of Helsinki of the World Medical Association. Results. Dynamics evaluation of endothelial function indicates a significant increase in blood flow in the brachial artery after compression in the NSTEMI group, but a decrease in the STEMI group after vasodilation of exogenous NO. Analysis of phospholipase A2 activity and paraoxonase showed an increasing the first in STEMI group compared to NSTEMI one and CCS while decreasing the second in the corresponding groups (Tab. 1). The results of the study confirm the association of increased activity of phospholipase A2 with vascular disorders severity, the correction of which should be considered a priority in prospective studies. The fact of reducing the activity of paraoxonase should be considered in the correction treatment of vascular disorders. Tab. 1 CCS NSTEMI STEMI LSD criteria D% 7,48 ± 0,39 6,65 ± 0,54 6,77 ± 0,62 {1-2} V% 54,71 ± 1,01 51,13 ± 1,92 42,16 ± 3,29 p1 < 0,0001 p2 = 0,010 {3} / {1, 2} D% (NO) 10,35 ± 0,47 8,24 ± 0,96 10,28 ± 0,98 {1, 2} V% (NO) 55,60 ± 1,12 37,71 ± 3,72 p1 < 0,0001 28,12 ± 3,94 p1 < 0,0001 {1} / {2, 3} sPA2 1,12 ± 0,03 1,25 ± 0,04 p1 < 0,0001 1,34 ± 0,04 p1 < 0,0001 {1} / {2, 3} PAO 0,54 ± 0,01 0,50 ± 0,01 0,44 ± 0,01 p1 < 0,0001 p2 < 0,0001 {1} / {2,3} D% - diameter of brachial artery after compression. V% - blood flow velocity after compression. sPA2 -phospholipase A2. PAO - paraoxanase. p - reliability on Sheffe"s criteria.

Download Full-text

Biological effects of ticagrelor over clopidogrel in patients with stable coronary artery disease and chronic obstructive pulmonary disease

Thrombosis and Haemostasis ◽

10.1160/th16-12-0973 ◽

2017 ◽

Vol 117 (06) ◽

pp. 1208-1216 ◽

Cited By ~ 26

Author(s):

Gianluca Campo ◽

Francesco Vieceli Dalla Sega ◽

Rita Pavasini ◽

Giorgio Aquila ◽

Francesco Gallo ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Function ◽

Pulmonary Disease ◽

Primary Endpoint ◽

Stable Coronary Artery Disease ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Artery Disease

SummaryPatients with SCAD and concomitant COPD are at high risk of cardiovascular adverse events, due to chronic inflammation, responsible of endothelial dysfunction, oxidative stress and heightened platelet reactivity (PR). The objective of this randomised clinical trial was to test if ticagrelor is superior to clopidogrel in improving endothelial function in patients with stable coronary artery disease (SCAD) and concomitant chronic obstructive pulmonary disease (COPD). Forty-six patients with SCAD and COPD undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (n=23) or ticagrelor (n=23) on top of standard therapy with aspirin. The following parameters were assessed at baseline and after 1 month: i) rate of apoptosis and ii) nitric oxide (NO) levels in human umbilical vein endothelial cells (HUVECs), iii) levels of reactive oxygen species (ROS) in peripheral blood mononuclear cell, iv) 29 cytokines/chemokines, v) on-treatment PR. The primary endpoint of the study was the 1-month rate of HUVECs apoptosis. The rate of apoptosis after 1 month was significantly lower in patients treated with ticagrelor (7.4 ± 1.3% vs 9.3 ± 1.5%, p<0.001), satisfying the pre-specified primary endpoint. In the ticagrelor arm, levels of NO were higher (10.1 ± 2.2 AU vs 8.5 ± 2.6 AU, p=0.03) while those of ROS (4 ± 1.8 AU vs 5.7 ± 2.8 AU, p=0.02) and P2Y12 reactivity units (52 ± 70 PRU vs 155 ± 62 PRU, p<0.001) were lower. There were no differences in cytokines/chemokines levels and aspirin reactivity units between groups. In patients with SCAD and COPD undergoing PCI, ticagrelor, as compared to clopidogrel is superior in improving surrogate markers of endothelial function and on-treatment PR (ClinicalTrials.gov, NCT02519608).Supplementary Material to this article is available online at www.thrombosis-online.com.

Download Full-text