Endothelial Function in COPD Is in an Intermediate Position Between Healthy Subjects and Coronary Artery Disease Patients and Is Related to Physical Activity

The disruption of endothelial homeostasis is the hallmark of coronary artery disease (CAD) and psychological disorders such as anxiety/depression. Xinkeshu (XKS), a traditional Chinese patent medicine, plays an essential role in CAD and psychological condition; however, the mechanisms underlying the effects of XKS on the endothelial function and endogenous endothelium-repair capacity in CAD patients with anxiety/depression remain elusive. In this study, endothelial function and endothelial progenitor cell- (EPC-) mediated reendothelialization capacity were compared among age-matched healthy subjects, CAD patients with or without anxiety/depression. Besides, CAD patients with anxiety/depression received 1-month XKS treatment. Anxiety/depression symptoms were evaluated by Generalized Anxiety Disorder 7-item (GAD-7)/Patient Health Questionnaire-9 (PHQ-9) score, endothelial function was tested by flow mediated dilation (FMD) measurement, and EPC-mediated reendothelialization capacity was evaluated by a carotid artery injury model in nude mouse ( n = 6 ) with the injection of XKS-incubated EPCs from CAD patients with anxiety/depression. The results showed that FMD and EPC-mediated reendothelialization capacity of CAD patients with anxiety/depression were compromised compared to healthy subjects and CAD patients without anxiety/depression. After 1 month of XKS treatment, FMD increased from 4.29 ± 1.65 to 4.87 ± 1.58 % ( P < 0.05 ) in CAD patients with anxiety/depression, whereas it remained unchanged in the controls. Moreover, XKS decreased GAD-7 and PHQ-9 scores. Meanwhile, incubating XKS enhanced in vivo reendothelialization capacity and in vitro apoptosis of EPCs from CAD patients with anxiety/depression, which was associated with the upregulation of CXC-chemokine receptor 7 (CXCR7) and inhibition of phosphorylation of p38 signaling. CXCR7 knockdown abolished the beneficial effects of XKS, which was rescued by p38 inhibitor SB203580. Our data demonstrate for the first time that XKS improves endothelial function and enhances EPC-mediated reendothelialization through CXCR7/p38/cleaved casepase-3 signaling and provides novel insight into the detailed mechanism of XKS in maintaining endothelial homeostasis in CAD patients with anxiety/depression.

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Regular Physical Activity Improves Endothelial Function in Patients With Coronary Artery Disease by Increasing Phosphorylation of Endothelial Nitric Oxide Synthase

Circulation ◽

10.1161/01.cir.0000074229.93804.5c ◽

2003 ◽

Vol 107 (25) ◽

pp. 3152-3158 ◽

Cited By ~ 565

Author(s):

R. Hambrecht ◽

V. Adams ◽

S. Erbs ◽

A. Linke ◽

N. Kränkel ◽

...

Keyword(s):

Physical Activity ◽

Nitric Oxide ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Nitric Oxide Synthase ◽

Endothelial Function ◽

Endothelial Nitric Oxide Synthase ◽

Artery Disease ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

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Habitual physical activity is associated with endothelial function and endothelial progenitor cells in patients with stable coronary artery disease

European Journal of Cardiovascular Prevention & Rehabilitation ◽

10.1097/hjr.0b013e32832b38be ◽

2009 ◽

Vol 16 (4) ◽

pp. 464-471 ◽

Cited By ~ 30

Author(s):

Ting-Hin Luk ◽

Yuk-Ling Dai ◽

Chung-Wah Siu ◽

Kai-Hang Yiu ◽

Hiu-Ting Chan ◽

...

Keyword(s):

Physical Activity ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Function ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Relative Increase ◽

Habitual Physical Activity ◽

Endothelial Progenitor ◽

Artery Disease

Background Exercise training reduces mortality in patients with coronary artery disease (CAD); however, the impact of habitual physical activity level (PAL) on vascular endothelial function and circulating endothelial progenitor cells (EPCs) remain unknown. Methods We assessed habitual PAL using a validated International Physical Activity Questionnaire in 116 patients (67.8 ± 9.5 years; 81% male) with stable CAD and preserved left ventricular ejection fraction ≥ 45%. The number of circulating CD34/KDR+ and CD133/KDR+ EPCs was determined by flow cytometry, and brachial artery flow-mediated dilation (FMD) was measured. Results The mean PAL of CAD patients with 1644 MET min/week (where MET is metabolic equivalents). With higher habitual PAL tertiles, there were significant linear trends of increased FMD ( P = 0.001) and CD133/KDR+ EPCs ( P = 0.03), but not of CD34/KDR+ EPCs. Patients with the highest tertile of PAL were associated with an absolute increase of 1.89% in FMD (relative increase 68%, P = 0.003) and 0.12% in CD133/KDR+ EPCs (relative increase 44%, P = 0.01) compared with those in the lowest tertile of PAL, after adjusting for age, sex, presence of hypertension, diabetes mellitus, hypercholesterolemia, smoking, and the use of medications including statins. However, neither CD34/KDR+ nor CD133/KDR+ EPCs significantly correlated with FMD. Conclusion This study showed that higher habitual PAL in patients with CAD was associated with higher FMD and EPC count. Nonetheless, FMD only significantly correlated with increased PAL, but not EPC, suggesting that increased physical activity improves endothelial function through mechanisms other than increasing EPC count.

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Noninvasive Visualization of Coronary Artery Endothelial Function in Healthy Subjects and in Patients With Coronary Artery Disease

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2010.06.036 ◽

2010 ◽

Vol 56 (20) ◽

pp. 1657-1665 ◽

Cited By ~ 85

Author(s):

Allison G. Hays ◽

Glenn A. Hirsch ◽

Sebastian Kelle ◽

Gary Gerstenblith ◽

Robert G. Weiss ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Function ◽

Healthy Subjects ◽

Artery Disease

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Physical activity in patients with coronary artery disease: effects on endothelial function and NAD(P)H oxidase-expression

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(02)80990-1 ◽

2002 ◽

Vol 39 ◽

pp. 222-223

Author(s):

Rainer Hambrecht ◽

Sandra Erbs ◽

Volker Adams ◽

Yves Baither ◽

Nicolle Kränkel ◽

...

Keyword(s):

Physical Activity ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Function ◽

Artery Disease

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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.

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Osteoprotegerin and Osteopontin Serum Levels are Associated with Vascular Function and Inflammation in Coronary Artery Disease Patients

Current Vascular Pharmacology ◽

10.2174/1570161117666191022095246 ◽

2020 ◽

Vol 18 (5) ◽

pp. 523-530 ◽

Cited By ~ 2

Author(s):

Konstantinos Maniatis ◽

Gerasimos Siasos ◽

Evangelos Oikonomou ◽

Manolis Vavuranakis ◽

Marina Zaromytidou ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Function ◽

Vascular Function ◽

Serum Levels ◽

Atherosclerosis Progression ◽

Control Subjects ◽

Significant Difference ◽

Artery Disease ◽

Stable Cad

Background: Osteoprotegerin and osteopontin have recently emerged as key factors in both vascular remodelling and atherosclerosis progression. Interleukin-6 (IL-6) is an inflammatory cytokine with a key role in atherosclerosis. The relationship of osteoprotegerin, osteopontin, and IL-6 serum levels with endothelial function and arterial stiffness was evaluated in patients with coronary artery disease (CAD). Methods: We enrolled 219 patients with stable CAD and 112 control subjects. Osteoprotegerin, osteopontin and IL-6 serum levels were measured using an ELISA assay. Endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery and carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Results: There was no significant difference between control subjects and CAD patients according to age and sex. Compared with control subjects, CAD patients had significantly impaired FMD (p<0.001) and increased PWV (p=0.009). CAD patients also had significantly higher levels of osteoprotegerin (p<0.001), osteopontin (p<0.001) and IL-6 (p=0.03), compared with control subjects. Moreover, IL-6 levels were correlated with osteoprotegerin (r=0.17, p=0.01) and osteopontin (r=0.30, p<0.001) levels. FMD was correlated with osteoprotegerin levels independent of possible confounders [b coefficient= - 0.79, 95% CI (-1.54, -0.05), p=0.04]. Conclusion: CAD patients have increased osteoprotegerin, osteopontin and IL-6 levels. Moreover, there is a consistent association between osteoprotegerin and osteopontin serum levels, vascular function and inflammation in CAD patients. These findings suggest another possible mechanism linking osteoprotegerin and osteopontin serum levels with CAD progression through arterial wall stiffening and inflammation.

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