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Article ; Online: Risk indexation and atrial fibrillation.

Nguyen, Thanh H / Heresztyn, Tamila / Horowitz, John D

Aging

2019 Volume 11, Issue 6, Page(s) 1607–1608

MeSH term(s)	Arginine ; Atrial Fibrillation ; Humans
Chemical Substances	Arginine (94ZLA3W45F)
Language	English
Publishing date	2019-03-28
Publishing country	United States
Document type	Editorial ; Comment
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.101889
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Article: Perhexiline Therapy in Patients with Type 2 Diabetes: Incremental Insulin Resistance despite Potentiation of Nitric Oxide Signaling.

Chong, Cher-Rin / Liu, Saifei / Imam, Hasan / Heresztyn, Tamila / Sallustio, Benedetta C / Chirkov, Yuliy Y / Horowitz, John D

Biomedicines

2022 Volume 10, Issue 10

Abstract: Perhexiline (Px) inhibits carnitine palmitoyltransferase 1 (CPT1), which controls uptake of long chain fatty acids into mitochondria. However, occasional cases of hypoglycaemia have been reported in Px-treated patients, raising the possibility that Px ... ...

Abstract	Perhexiline (Px) inhibits carnitine palmitoyltransferase 1 (CPT1), which controls uptake of long chain fatty acids into mitochondria. However, occasional cases of hypoglycaemia have been reported in Px-treated patients, raising the possibility that Px may also increase sensitivity to insulin. Furthermore, Px increases anti-aggregatory responses to nitric oxide (NO), an effect which may theoretically parallel insulin sensitization. We therefore sought to examine these relationships in patients with stable Type 2 diabetes (T2D) and cardiovascular disease (n = 30). Px was initiated, and dosage was titrated, to reach the therapeutic range and thus prevent toxicity. Investigations were performed before and after 2 weeks, to examine changes in insulin sensitivity and, utilizing aggregometry in whole blood, platelet responsiveness to the anti-aggregatory effects of the NO donor sodium nitroprusside (SNP). Other parameters that affect may affect NO signalling were also evaluated. Px substantially potentiated inhibition of platelet aggregation by SNP (from 16.7 ± 3.0 to 27.3 ± 3.7%;
Language	English
Publishing date	2022-09-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10102381
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Article ; Online: Impairment of platelet NO signalling in coronary artery spasm: role of hydrogen sulphide.

Imam, Hasan / Nguyen, Thanh H / Stafford, Irene / Liu, Saifei / Heresztyn, Tamila / Chirkov, Yuliy Y / Horowitz, John D

British journal of pharmacology

2021 Volume 178, Issue 7, Page(s) 1639–1650

Abstract: Background and purpose: The pathophysiology of coronary artery spasm (CAS), with its associated ischaemic crises, is currently poorly understood and treatment is frequently ineffective. In view of increasing evidence that platelet-based defects may ... ...

Abstract	Background and purpose: The pathophysiology of coronary artery spasm (CAS), with its associated ischaemic crises, is currently poorly understood and treatment is frequently ineffective. In view of increasing evidence that platelet-based defects may occur in CAS patients, we investigated platelet reactivity in CAS patients and whether symptomatic crises reflect activation of platelet-endothelial interactions. Experimental approach: CAS patients were evaluated during acute and/or chronic symptomatic phases and compared with healthy control subjects. Inhibition of ADP-induced platelet aggregation by the NO donor sodium nitroprusside (SNP) and plasma concentrations of syndecan 1 (glycocalyx shedding marker), tryptase (mast cell activation marker) and platelet microparticles were measured. Key results: Inhibition of platelet aggregation by SNP was diminished in chronic CAS, with further (non-significant) deterioration during symptomatic crises, whereas plasma concentrations of syndecan 1, tryptase and platelet microparticles increased. Treatment of patients with high-dose N-acetylcysteine (NAC) plus glyceryl trinitrate rapidly increased platelet responsiveness to SNP and decreased plasma syndecan 1 concentrations. The effect of NAC on platelet responsiveness to SNP was confirmed in vitro and mimicked by the H Conclusion and implications: CAS is associated with substantial impairment of platelet NO signalling. During acute symptomatic exacerbations, platelet resistance to NO is aggravated, together with mast cell activation and damage to both vasculature and platelets. NAC, via release of H
MeSH term(s)	Blood Platelets ; Coronary Vessels ; Humans ; Hydrogen Sulfide/pharmacology ; Platelet Aggregation ; Platelet Aggregation Inhibitors/pharmacology ; Spasm
Chemical Substances	Platelet Aggregation Inhibitors ; Hydrogen Sulfide (YY9FVM7NSN)
Language	English
Publishing date	2021-02-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.15388
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Article: An overview of plasma concentrations of asymmetric dimethylarginine (ADMA) in health and disease and in clinical studies: methodological considerations.

Horowitz, John D / Heresztyn, Tamila

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

2007 Volume 851, Issue 1-2, Page(s) 42–50

Abstract: Recent studies among patients including those with known coronary disease demonstrate that small elevations in asymmetric dimethylarginine (ADMA) concentrations in plasma are predictive of adverse outcomes. The precision of current methodologies for ... ...

Abstract	Recent studies among patients including those with known coronary disease demonstrate that small elevations in asymmetric dimethylarginine (ADMA) concentrations in plasma are predictive of adverse outcomes. The precision of current methodologies for quantitation of ADMA such as HPLC, MS and ELISA is discussed with respect to many reports which appear to over-estimate ADMA levels and quote broad concentration ranges. While plasma ADMA concentrations tend to increase with age, the mean for a healthy population is between 0.4 and 0.6 microM. ADMA levels may fluctuate in normal subjects, and this needs to be considered in light of the relatively small differences in ADMA concentration between healthy normal subjects and patients.
MeSH term(s)	Animals ; Arginine/analogs & derivatives ; Arginine/blood ; Chromatography, High Pressure Liquid ; Clinical Laboratory Techniques ; Disease ; Health ; Humans ; Mass Spectrometry
Chemical Substances	N,N-dimethylarginine (63CV1GEK3Y) ; Arginine (94ZLA3W45F)
Language	English
Publishing date	2007-05-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1570-0232
ISSN	1570-0232
DOI	10.1016/j.jchromb.2006.09.023
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Article ; Online: Endothelial dysfunction and glycocalyx shedding in heart failure: insights from patients receiving cardiac resynchronisation therapy.

Ajaero, Chukwudiebube N / Procter, Nathan E K / Chirkov, Yuliy Y / Heresztyn, Tamila / Arstall, Margaret A / McGavigan, Andrew D / Frenneaux, Michael P / Horowitz, John D

Heart and vessels

2019 Volume 35, Issue 2, Page(s) 197–206

Abstract: To determine (a) whether chronic heart failure with reduced ejection fraction (HFrEF) is associated with increased glycocalyx shedding; (b) whether glycocalyx shedding in HFrEF with left ventricular dyssynchrony is related to inflammation, endothelial ... ...

Abstract	To determine (a) whether chronic heart failure with reduced ejection fraction (HFrEF) is associated with increased glycocalyx shedding; (b) whether glycocalyx shedding in HFrEF with left ventricular dyssynchrony is related to inflammation, endothelial dysfunction and/or redox stress and is ameliorated by cardiac resynchronisation therapy. Glycocalyx shedding has been reported to be increased in heart failure and is a marker of increased mortality. Its role in dyssynchronous systolic heart failure and the effects of cardiac resynchronisation therapy (CRT) are largely unknown. Twenty-six patients with dyssynchronous HFrEF were evaluated before and 6 months after CRT insertion. Echocardiographic septal to posterior wall delay (SPWD) assessed intra-ventricular mechanical dyssynchrony, and quality of life, integrity of nitric oxide (NO) signalling, inflammatory and redox-related biomarkers were measured. Glycocalyx shedding was quantitated via plasma levels of the glycocalyx component, syndecan-1. Syndecan-1 levels pre-CRT were inversely correlated with LVEF (r = - 0.45, p = 0.02) and directly with SPWD (r = 0.44, p = 0.02), QOL (r = 0.39, p = 0.04), plasma NT-proBNP (r = 0.43, p = 0.02), and the inflammatory marker, symmetric dimethylarginine (SDMA) (r = 0.54, p = 0.003). On multivariate analysis, syndecan-1 levels were predicted by SPWD and SDMA (β = 0.42, p = 0.009 and β = 0.54, p = 0.001, respectively). No significant correlation was found between syndecan-1 levels and other markers of endothelial dysfunction/inflammatory activation. Following CRT there was no significant change in syndecan-1 levels. In patients with dyssynchronous HFrEF, markers of glycocalyx shedding are associated with the magnitude of mechanical dyssynchrony and elevation of SDMA levels and inversely with LVEF. However, CRT does not reverse this process.
MeSH term(s)	Aged ; Biomarkers/blood ; Cardiac Resynchronization Therapy ; Chronic Disease ; Endothelial Cells/metabolism ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiopathology ; Female ; Glycocalyx/metabolism ; Heart Failure, Systolic/blood ; Heart Failure, Systolic/diagnosis ; Heart Failure, Systolic/physiopathology ; Heart Failure, Systolic/therapy ; Humans ; Male ; Stroke Volume ; Syndecan-1/blood ; Time Factors ; Treatment Outcome ; Ventricular Dysfunction, Left/blood ; Ventricular Dysfunction, Left/diagnosis ; Ventricular Dysfunction, Left/physiopathology ; Ventricular Dysfunction, Left/therapy ; Ventricular Function, Left
Chemical Substances	Biomarkers ; SDC1 protein, human ; Syndecan-1
Language	English
Publishing date	2019-08-27
Publishing country	Japan
Document type	Journal Article
ZDB-ID	89678-0
ISSN	1615-2573 ; 0910-8327 ; 0935-736X
ISSN (online)	1615-2573
ISSN	0910-8327 ; 0935-736X
DOI	10.1007/s00380-019-01481-3
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Article ; Online: Asymmetric and Symmetric Dimethylarginine Predict Outcomes in Patients With Atrial Fibrillation: An ARISTOTLE Substudy.

Horowitz, John D / De Caterina, Raffaele / Heresztyn, Tamila / Alexander, John H / Andersson, Ulrika / Lopes, Renato D / Steg, Philippe Gabriel / Hylek, Elaine M / Mohan, Puneet / Hanna, Michael / Jansky, Petr / Granger, Christopher B / Wallentin, Lars

Journal of the American College of Cardiology

2018 Volume 72, Issue 7, Page(s) 721–733

Abstract: Background: There is little mechanistic information on factors predisposing atrial fibrillation (AF) patients to thromboembolism or bleeding, but generation of nitric oxide (NO) might theoretically contribute to both.: Objectives: The authors tested ... ...

Abstract	Background: There is little mechanistic information on factors predisposing atrial fibrillation (AF) patients to thromboembolism or bleeding, but generation of nitric oxide (NO) might theoretically contribute to both. Objectives: The authors tested the hypothesis that plasma levels of the methylated arginine derivatives asymmetric and symmetric dimethylarginine (ADMA/SDMA), which inhibit NO generation, might be associated with outcomes in AF. Methods: Plasma samples were obtained from 5,004 patients with AF at randomization to warfarin or apixaban in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. ADMA and SDMA concentrations were measured by high-performance liquid chromatography. Relationships to clinical characteristics were evaluated by multivariable analyses. Associations with major outcomes, during a median of 1.9 years follow-up, were evaluated by adjusted Cox proportional hazards models. Results: Both ADMA and SDMA plasma concentrations at study entry increased significantly with patients' age, female sex, renal impairment, permanent AF, or congestive heart failure. ADMA and SDMA increased (p < 0.001) with both increased CHA Conclusions: In anticoagulated patients with AF, elevated ADMA levels are weakly associated with thromboembolic events, elevated SDMA levels with bleeding events and both are strongly associated with increased mortality. These findings suggest that disturbances of NO function modulate both thrombotic and hemorrhagic risk in anticoagulated patients with AF. (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]; NCT00412984).
MeSH term(s)	Aged ; Aged, 80 and over ; Anticoagulants/therapeutic use ; Arginine/analogs & derivatives ; Arginine/blood ; Atrial Fibrillation/blood ; Atrial Fibrillation/diagnosis ; Atrial Fibrillation/drug therapy ; Biomarkers/blood ; Double-Blind Method ; Factor Xa Inhibitors/therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Pyrazoles/therapeutic use ; Pyridones/therapeutic use ; Treatment Outcome ; Warfarin/therapeutic use
Chemical Substances	Anticoagulants ; Biomarkers ; Factor Xa Inhibitors ; Pyrazoles ; Pyridones ; apixaban (3Z9Y7UWC1J) ; symmetric dimethylarginine (49787G1ULV) ; Warfarin (5Q7ZVV76EI) ; N,N-dimethylarginine (63CV1GEK3Y) ; Arginine (94ZLA3W45F)
Language	English
Publishing date	2018-08-09
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	605507-2
ISSN	1558-3597 ; 0735-1097
ISSN (online)	1558-3597
ISSN	0735-1097
DOI	10.1016/j.jacc.2018.05.058
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Article ; Online: Mechanisms Responsible for Serotonin Vascular Reactivity Sex Differences in the Internal Mammary Artery.

Lamin, Victor / Jaghoori, Amenah / Jakobczak, Rachel / Stafford, Irene / Heresztyn, Tamila / Worthington, Michael / Edwards, James / Viana, Fabiano / Stuklis, Robert / Wilson, David P / Beltrame, John F

Journal of the American Heart Association

2018 Volume 7, Issue 14

Abstract: Background: The increased adverse cardiac events in women undergoing coronary artery bypass grafting are multifactorial and may include clinical, psychosocial, and biological factors. Potential contributing biological factors could include vascular ... ...

Abstract	Background: The increased adverse cardiac events in women undergoing coronary artery bypass grafting are multifactorial and may include clinical, psychosocial, and biological factors. Potential contributing biological factors could include vascular hyperreactivity of the internal mammary artery (IMA) to endogenous vasoconstrictors in women, resulting in a predilection to myocardial ischemia. This study evaluated sex differences in serotonin and thromboxane A Methods and results: Viable isolated human IMA segments were obtained from 116 patients (44 women [mean age, 66.8±12.2 years] and 72 men [mean age, 66.6±10.4 years]) undergoing coronary artery bypass grafting. Cumulative concentration-response curves for serotonin and thromboxane A Conclusions: These data indicate that female IMAs are hyperreactive to serotonin but not U46619, with the former attributable to an endothelium-dependent cyclooxygenase pathway.
MeSH term(s)	15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology ; Aged ; Coronary Artery Bypass ; Cyclooxygenase Inhibitors/pharmacology ; Endothelium, Vascular/drug effects ; Female ; Humans ; Male ; Mammary Arteries/drug effects ; Mammary Arteries/physiology ; Middle Aged ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/antagonists & inhibitors ; Nitric Oxide Synthase Type III/metabolism ; Prostaglandin-Endoperoxide Synthases/metabolism ; Prostaglandins/metabolism ; Serotonin/pharmacology ; Serotonin Receptor Agonists/pharmacology ; Sex Characteristics ; Thromboxane A2 ; Vasoconstriction/drug effects ; Vasoconstrictor Agents/pharmacology
Chemical Substances	Cyclooxygenase Inhibitors ; Prostaglandins ; Serotonin Receptor Agonists ; Vasoconstrictor Agents ; Nitric Oxide (31C4KY9ESH) ; Serotonin (333DO1RDJY) ; Thromboxane A2 (57576-52-0) ; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid (76898-47-0) ; NOS3 protein, human (EC 1.14.13.39) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Prostaglandin-Endoperoxide Synthases (EC 1.14.99.1)
Language	English
Publishing date	2018-07-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.117.007126
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Article ; Online: Reversal of hyperglycemia: effects on nitric oxide signaling.

Chong, Cher-Rin / Liu, Saifei / Licari, Giovanni / Heresztyn, Tamila / Chirkov, Yuliy Y / Ngo, Doan T / Horowitz, John D

The American journal of medicine

2015 Volume 128, Issue 4, Page(s) 427–430

Abstract: Background: Hyperglycemia in patients with acute coronary syndromes is associated with poor outcomes, and its rapid correction with insulin infusion has been shown to restore platelet responsiveness to nitric oxide and to suppress superoxide (O2(-)) ... ...

Abstract	Background: Hyperglycemia in patients with acute coronary syndromes is associated with poor outcomes, and its rapid correction with insulin infusion has been shown to restore platelet responsiveness to nitric oxide and to suppress superoxide (O2(-)) generation. Thioredoxin-interacting protein has emerged recently as a pivotal modulator of hyperglycemia-induced inflammation, O2(-) production, and impairment of nitric oxide signaling, but it is not known whether its expression in platelets can be downregulated rapidly. Methods: In 12 hyperglycemic patients with acute coronary syndrome, we evaluated the putative role of thioredoxin-interacting protein suppression in the platelet nitric oxide response after reversal of hyperglycemia with insulin infusion. Results: Insulin infusion for 13.0 ± 0.8 (standard error of the mean) hours decreased blood glucose level from 16.6 ± 1.6 mmol/L to 8.7 ± 1.4 mmol/L (P = .002). This induced (1) sensitization of antiaggregatory response to nitric oxide (from 6.5% ± 7.7% to 39.7% ± 7.0%, P < .0001); (2) improved endothelial progenitor cell function (from a median of 45 to 180 colony-forming units, P < .05); and (3) decreases of whole blood reactive oxygen species content (P < .05). However, there was no significant suppression of platelet thioredoxin-interacting protein expression (mean decrease, 59 arbitrary units; 95% confidence interval, -193 to +74). Conclusions: Correction of hyperglycemia in patients with acute coronary syndrome rapidly reverses oxidative stress, restoring both platelet nitric oxide responsiveness and endothelial progenitor cell function, but this process is largely or entirely independent of thioredoxin-interacting protein.
MeSH term(s)	Acute Coronary Syndrome/complications ; Acute Coronary Syndrome/metabolism ; Acute Coronary Syndrome/physiopathology ; Aged ; Blood Glucose/metabolism ; Blood Platelets/metabolism ; Carrier Proteins/drug effects ; Carrier Proteins/metabolism ; Creatine Kinase/blood ; Down-Regulation ; Endothelial Progenitor Cells/metabolism ; Female ; Glycated Hemoglobin A/metabolism ; Humans ; Hyperglycemia/blood ; Hyperglycemia/drug therapy ; Hypoglycemic Agents/administration & dosage ; Infusions, Intravenous ; Insulin/administration & dosage ; Male ; Middle Aged ; Nitric Oxide/metabolism ; Oxidative Stress/drug effects ; Platelet Aggregation/drug effects ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; Troponin T/blood
Chemical Substances	Blood Glucose ; Carrier Proteins ; Glycated Hemoglobin A ; Hypoglycemic Agents ; Insulin ; Reactive Oxygen Species ; TXNIP protein, human ; Troponin T ; hemoglobin A1c protein, human ; Nitric Oxide (31C4KY9ESH) ; Creatine Kinase (EC 2.7.3.2)
Language	English
Publishing date	2015-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80015-6
ISSN	1555-7162 ; 1873-2178 ; 0002-9343 ; 1548-2766
ISSN (online)	1555-7162 ; 1873-2178
ISSN	0002-9343 ; 1548-2766
DOI	10.1016/j.amjmed.2014.11.007
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Article ; Online: Endothelial function, oxidative stress and inflammatory studies in chronic coronary slow flow phenomenon patients.

Kopetz, Victoria / Kennedy, Jennifer / Heresztyn, Tamila / Stafford, Irene / Willoughby, Scott R / Beltrame, John F

Cardiology

2012 Volume 121, Issue 3, Page(s) 197–203

Abstract: The coronary slow flow phenomenon (CSFP) is associated with coronary microvascular dysfunction although the responsible mechanisms are unknown. This study compared endothelial function assessed by changes in augmentation index (AIx) following endothelium- ...

Abstract	The coronary slow flow phenomenon (CSFP) is associated with coronary microvascular dysfunction although the responsible mechanisms are unknown. This study compared endothelial function assessed by changes in augmentation index (AIx) following endothelium-independent (glyceryl trinitrate, GTN) and endothelium-dependent vasodilators (salbutamol), in 40 stable CSFP patients and 23 age-matched healthy controls. Plasma concentrations of inflammatory proteins (myeloperoxidase and high-sensitivity C-reactive protein), oxidative stress biomarkers (malondialdehyde and homocysteine), and asymmetric dimethylarginine levels were also determined. There were no differences between CSFP and controls in response to salbutamol (AIx: -2.28 ± 0.88% vs. -3.22 ± 0.70%, p = 0.4) or GTN (AIx: -11.30 ± 0.75% vs. -13.30 ± 1.00%, p = 0.12). Similarly, there were no differences in the measured biomarkers. Thus, alternate mechanisms to the assessed endothelial function, inflammatory and oxidative stress processes should be explored to explain the microvascular dysfunction in CSFP patients.
MeSH term(s)	Adrenergic beta-2 Receptor Agonists/therapeutic use ; Aged ; Albuterol/therapeutic use ; Biomarkers/blood ; Coronary Disease/drug therapy ; Coronary Disease/physiopathology ; Endothelium, Vascular/physiology ; Female ; Humans ; Male ; Microcirculation/physiology ; Middle Aged ; Nitroglycerin/therapeutic use ; No-Reflow Phenomenon/drug therapy ; No-Reflow Phenomenon/physiopathology ; Oxidative Stress/physiology ; Prospective Studies ; Vasodilator Agents/therapeutic use
Chemical Substances	Adrenergic beta-2 Receptor Agonists ; Biomarkers ; Vasodilator Agents ; Nitroglycerin (G59M7S0WS3) ; Albuterol (QF8SVZ843E)
Language	English
Publishing date	2012
Publishing country	Switzerland
Document type	Controlled Clinical Trial ; Journal Article
ZDB-ID	80092-2
ISSN	1421-9751 ; 0008-6312
ISSN (online)	1421-9751
ISSN	0008-6312
DOI	10.1159/000336948
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Article ; Online: Interactions between inflammatory activation and endothelial dysfunction selectively modulate valve disease progression in patients with bicuspid aortic valve.

Ali, Onn Akbar / Chapman, Matthew / Nguyen, Thanh Ha / Chirkov, Yuliy Y / Heresztyn, Tamila / Mundisugih, Juan / Horowitz, John D

Heart (British Cardiac Society)

2014 Volume 100, Issue 10, Page(s) 800–805

Abstract: Objectives: Bicuspid aortic valve (BAV) is associated with increased risk of valvular degeneration and ascending aortic aneurysm formation and rupture. We sought to evaluate the roles of endothelial dysfunction and inflammatory activation in modulating ... ...

Abstract	Objectives: Bicuspid aortic valve (BAV) is associated with increased risk of valvular degeneration and ascending aortic aneurysm formation and rupture. We sought to evaluate the roles of endothelial dysfunction and inflammatory activation in modulating these processes. Methods: We performed a case-control study of patients with BAV together with a multivariate analysis within the BAV group to identify factors associated with: development of significant valvular disease; dilatation of the ascending aorta; differential valve relative to aortic disease. Endothelial function of patients and controls was evaluated via flow-mediated dilatation (FMD) and plasma concentrations of asymmetric dimethylarginine (ADMA). Correlations with inflammatory markers and endothelial progenitor cell counts were also examined. Morphological and physiological assessment of the valve and ascending aorta was performed with transthoracic echocardiography and MRI. Results: Patients with BAV (n=43) and controls (n=25) were matched for age and gender. FMD was significantly lower in patients than controls (7.85±3.48% vs 11.58±3.98%, p=0.001), and these differences were age-independent. Within the BAV cohort, multivariate correlates of peak aortic valve velocity were plasma concentrations of ADMA and myeloperoxidase (MPO) (both p<0.01), while increasing age was an independent correlate of ascending aortic diameter (p<0.05). Furthermore, both low FMD and inflammatory activation were multivariate correlates of selectivity for valvular disease. Conclusions: BAV is associated with endothelial dysfunction. The extent of inflammatory activation (specifically MPO release) and that of endothelial dysfunction impact primarily on integrity of the valve rather than aortic structure.
MeSH term(s)	Aorta/diagnostic imaging ; Aorta/physiopathology ; Aortic Valve/abnormalities ; Aortic Valve/metabolism ; Aortic Valve/physiopathology ; Arginine/analogs & derivatives ; Arginine/blood ; Bicuspid Aortic Valve Disease ; Biomarkers/metabolism ; Disease Progression ; Echocardiography ; Endothelium, Vascular/diagnostic imaging ; Endothelium, Vascular/physiopathology ; Female ; Follow-Up Studies ; Heart Valve Diseases/diagnosis ; Heart Valve Diseases/metabolism ; Heart Valve Diseases/physiopathology ; Humans ; Inflammation/metabolism ; Magnetic Resonance Imaging, Cine ; Male ; Middle Aged ; Nitric Oxide Synthase/antagonists & inhibitors ; Peroxidase/blood ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Vasodilation/physiology
Chemical Substances	Biomarkers ; N,N-dimethylarginine (63CV1GEK3Y) ; Arginine (94ZLA3W45F) ; Peroxidase (EC 1.11.1.7) ; Nitric Oxide Synthase (EC 1.14.13.39)
Language	English
Publishing date	2014-02-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1303417-0
ISSN	1468-201X ; 1355-6037
ISSN (online)	1468-201X
ISSN	1355-6037
DOI	10.1136/heartjnl-2014-305509
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In stock of ZB MED Cologne/Königswinter

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More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito