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

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.

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Endothelial Dysfunction, the Renin‐Angiotensin System, and Nitric Oxide: Impact on Coronary Artery Disease and Therapeutic Interventions

Clinical Cardiology ◽

10.1002/j.1932-8737.1997.tb00005.x ◽

1997 ◽

Vol 20 (S2) ◽

Keyword(s):

Nitric Oxide ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Dysfunction ◽

Renin Angiotensin System ◽

Therapeutic Interventions ◽

Angiotensin System ◽

Renin Angiotensin ◽

Artery Disease

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CD14+CD16++ “nonclassical” monocytes are associated with endothelial dysfunction in patients with coronary artery disease

Thrombosis and Haemostasis ◽

10.1160/th16-08-0614 ◽

2017 ◽

Vol 117 (05) ◽

pp. 971-980 ◽

Cited By ~ 27

Author(s):

Karol Urbanski ◽

Dominik Ludew ◽

Grzegorz Filip ◽

Magdalena Filip ◽

Agnieszka Sagan ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Mononuclear Cells ◽

Vascular Dysfunction ◽

Activation Markers ◽

Mammary Arteries ◽

No Bioavailability ◽

Artery Disease

SummaryEndothelial dysfunction and inflammation are key mechanisms of vascular disease. We hypothesised that heterogeneity of monocyte subpopulations may be related to the development of vascular dysfunction in coronary artery disease (CAD). Therefore, we examined the relationships between monocyte subsets (CD14++CD16– “classical – Mon1”, CD14++CD16+ “intermediate – Mon2” and CD14+CD16++ “nonclassical – Mon3”), endothelial function and risk factor profiles in 130 patients with CAD undergoing coronary artery bypass grafting. This allowed for direct nitric oxide (NO) bioavailability assessment using isometric tension studies ex vivo (acetylcholine; ACh- and sodium- nitropruside; SNP-dependent) in segments of internal mammary arteries. The expression of CD14 and CD16 antigens and activation markers were determined in peripheral blood mononuclear cells using flow cytometry. Patients with high CD14+CD16++ “nonclassical” and low CD14++CD16- “classical” monocytes presented impaired endothelial function. High frequency of CD14+CD16++ “nonclassical” monocytes was associated with increased vascular superoxide production. Furthermore, endothelial dysfunction was associated with higher expression of activation marker CD11c selectively on CD14+CD16++ monocytes. Nonclassical and classical monocyte frequencies remained independent predictors of endothelial dysfunction when major risk factors for atherosclerosis were taken into account (β =0.18 p=0.04 and β =-0.19 p=0.03, respectively). In summary, our data indicate that CD14+CD16++ “nonclassical” monocytes are associated with more advanced vascular dysfunction measured as NO-bioavailability and vascular reactive oxygen species production.

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

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(16)32336-1 ◽

2016 ◽

Vol 67 (13) ◽

pp. 2335

Author(s):

Gerasimos Siasos ◽

Evangelos Oikonomou ◽

Marina Zaromitidou ◽

Sotirios Tsalamandris ◽

Konstantinos Mourouzis ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Arterial Stiffness ◽

Endothelial Function ◽

Phospholipase A2 ◽

Stable Coronary Artery Disease ◽

Artery Disease

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LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 LEVELS, ENDOTHELIAL DYSFUNCTION AND ARTERIAL STIFFNESS IN PATIENTS WITH STABLE CORONARY ARTERY DISEASELIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 LEVELS, ENDOTHELIAL DYSFUNCTION AND ARTERIAL STIFFNESS IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(20)30777-4 ◽

2020 ◽

Vol 75 (11) ◽

pp. 150

Author(s):

Evangelos Oikonomou ◽

Konstantinos Mourouzis ◽

Gerasimos Siasos ◽

Marina Zaromitidou ◽

Vicky Tsigkou ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Dysfunction ◽

Arterial Stiffness ◽

Phospholipase A2 ◽

Stable Coronary Artery Disease ◽

Artery Disease

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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.

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