Evaluation of the Impact of Treatment on Endothelial Function and Cardiac Performance in Acromegaly

AbstractThis study addressed the hypothesis that epoxyeicosatrienoic acids (EETs) synthesized by CYP450 and catabolized by soluble epoxide hydrolase (sEH) are involved in the maintenance of renal allograft function, either directly or through modulation of cardiovascular function. The impact of single nucleotide polymorphisms (SNPs) in the sEH gene EPHX2 and CYP450 on renal and vascular function, plasma levels of EETs and peripheral blood monuclear cell sEH activity was assessed in 79 kidney transplant recipients explored at least one year after transplantation. Additional experiments in a mouse model mimicking the ischemia–reperfusion (I/R) injury suffered by the transplanted kidney evaluated the cardiovascular and renal effects of the sEH inhibitor t-AUCB administered in drinking water (10 mg/l) during 28 days after surgery. There was a long-term protective effect of the sEH SNP rs6558004, which increased EET plasma levels, on renal allograft function and a deleterious effect of K55R, which increased sEH activity. Surprisingly, the loss-of-function CYP2C9*3 was associated with a better renal function without affecting EET levels. R287Q SNP, which decreased sEH activity, was protective against vascular dysfunction while CYP2C8*3 and 2C9*2 loss-of-function SNP, altered endothelial function by reducing flow-induced EET release. In I/R mice, sEH inhibition reduced kidney lesions, prevented cardiac fibrosis and dysfunction as well as preserved endothelial function. The preservation of EET bioavailability may prevent allograft dysfunction and improve cardiovascular disease in kidney transplant recipients. Inhibition of sEH appears thus as a novel therapeutic option but its impact on other epoxyfatty acids should be carefully evaluated.

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The impact of obstructive sleep apnea on endothelial function during weight loss in an obese pediatric population

Sleep Medicine ◽

10.1016/j.sleep.2021.08.002 ◽

2021 ◽

Author(s):

Sofie Jacobs ◽

Emilie Mylemans ◽

Marijke Ysebaert ◽

Eline Vermeiren ◽

Ann De Guchtenaere ◽

...

Keyword(s):

Weight Loss ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Endothelial Function ◽

Pediatric Population ◽

Obstructive Sleep ◽

The Impact

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The impact of third-generation Beta-blocker antihypertensive treatment on endothelial function and the prothrombotic stateEffects of smoking

American Journal of Hypertension ◽

10.1016/j.amjhyper.2004.03.668 ◽

2004 ◽

Vol 17 (7) ◽

pp. 582-589 ◽

Cited By ~ 24

Author(s):

G VYSSOULIS

Keyword(s):

Endothelial Function ◽

Beta Blocker ◽

Antihypertensive Treatment ◽

Third Generation ◽

The Impact

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Comparison between the effects of mixed dyslipidaemia and hypercholesterolaemia on endothelial function, atherosclerotic lesions and fibrinolysis in rabbits

Clinical Science ◽

10.1042/cs1040357 ◽

2003 ◽

Vol 104 (4) ◽

pp. 357-365 ◽

Cited By ~ 9

Author(s):

Natalia de las HERAS ◽

Eva CEDIEL ◽

M. Pilar OUBIÑA ◽

Paloma ARAGONCILLO ◽

David SANZ-ROSA ◽

...

Keyword(s):

Endothelial Function ◽

Receptor Antagonist ◽

Plasminogen Activator ◽

Vascular Function ◽

Harmful Effect ◽

Tissue Type ◽

Vascular Structure ◽

Similar Increase ◽

The Impact ◽

Pai 1

We compared the impact of hypercholesterolaemia and mixed dyslipidaemia on vascular function, vascular structure and fibrinolytic balance in rabbits. To this end, vascular reactivity was studied in aortic rings from rabbits fed a control diet, a diet containing 0.5% cholesterol+14% coconut oil (mixed dyslipidaemia) or a diet containing 1% cholesterol (hypercholesterolaemia) for 12–14 weeks. Morphometric analysis of aorta was also performed and plasminogen activator inhibitor-1 (PAI-1) as well as tissue-type plasminogen activator (t-PA) plasma activities were measured. Both diets induced a similar increase in cholesterol plasma levels, although triacylglycerols (triglycerides) were increased in animals with mixed dyslipidaemia. Hypercholesterolaemia was associated with intimal thickening, reduction in acetylcholine-induced relaxation (P<0.05) and increased vasoconstriction induced by acetylcholine+NG-nitro-L-arginine methyl ester (L-NAME) when compared with controls (P<0.05). These effects were more marked (P<0.05) in animals with mixed dyslipidaemia. Incubation with ifetroban, a thromboxane A2/prostaglandin H2 receptor antagonist, increased acetylcholine-induced relaxation (P<0.05) and reduced acetylcholine+L-NAME contraction (P<0.05) in both diet groups. In contrast, the presence of PD 145, an endothelin (ET)A/ETB receptor antagonist, exerted these effects only in rabbits with mixed dyslipidaemia. Both hypercholesterolaemia and mixed dyslipidaemia induced a similar increase in PAI-1 and a similar decrease in t-PA plasma activities. These data suggest that hypertriglyceridaemia can increase the deleterious effects of hypercholesterolaemia on endothelial function and vascular structure. This additional harmful effect exerted by triacylglycerols on endothelial function could, in part, be mediated by ET.

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Retrospective Analysis of Endocrine Dysfunctions in a Population of Adult Polytransfused Patients: Correlation of GH-IGF1 Axis Alteration with Cardiac Performance

BioMed Research International ◽

10.1155/2018/6047801 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7

Author(s):

Michela Rosaria Campo ◽

Anna Farese ◽

Michele Correale ◽

Giuseppe Berti ◽

Michela Massa ◽

...

Keyword(s):

Intervention Study ◽

Adult Population ◽

Cardiac Performance ◽

Arginine Test ◽

Hormonal Evaluation ◽

The Impact ◽

Ghrh Plus Arginine Test ◽

Gh Deficit ◽

Endocrine Complications

Endocrine complications of haemochromatosis and heart failure mostly affect morbidity and mortality in polytransfused patients. This study analyzes endocrine dysfunctions and the impact of GH-IGF-1 axis alteration on cardiac performance in a population of 31 patients. A retrospective study on 31 Caucasian polytransfused outpatients, 27 adults and 4 pediatric, residing in Apulia, Italy, followed from 2005 to 2016, was conducted. Patients underwent basal and dynamic hormonal evaluation. GHRH plus arginine test was performed in 21 patients (19 adults and 2 children). Among them, 9 patients were affected by left ventricle diastolic dysfunction and/or atrial or ventricular dilatation (HD group) and 12 patients did not have cardiovascular disease (non-HD group). Twenty-nine out of 31 patients (94%) had at least one endocrinopathy. We found severe or mild GH deficit (GHD) in all HD patients versus 3 patients in the non-HD group (p=0.001). Mean IGF-1 levels were significantly lower in the HD group than in non-HD subjects (53±30 versus 122±91 μg/L, p=0.04). Our study confirms the need to perform a dynamic evaluation of the GH-IGF1 axis in polytransfused patients, especially when heart dysfunction emerges. An intervention study with GH replacement therapy in a larger randomized adult population will clarify the role of GH/IGF axis on cardiovascular outcomes in this patient population.

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Abstract 4688: The Impact of Marfan Syndrome on Arterial Stiffness and Endothelial Function: The Role of Matrix Metalloproteinases

Circulation ◽

10.1161/circ.118.suppl_18.s_930-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Stella Brilli ◽

Dimitris Tousoulis ◽

Charalambos Antoniades ◽

George Hatzis ◽

Nikos Ioakeimidis ◽

...

Keyword(s):

Matrix Metalloproteinases ◽

Arterial Stiffness ◽

Endothelial Function ◽

Marfan Syndrome ◽

Augmentation Index ◽

Flow Mediated Dilation ◽

Arterial Tree ◽

Augmentation Pressure ◽

The Impact

Background: Marfan syndrome is characterised by high risk of aortic dissections and increased cardiovascular risk. However, the impact of Marfan syndrome on endothelial function and arterial stiffness is unclear, while the role of matrix metalloproteinases is unknown. We examined the impact of Marfan syndrome on the elastic properties of the arterial tree, and vascular endothelial function, and we evaluated the potential role of matrix metalloproteinases in these effects. Methods: The study population consisted of 17 subjects with Marfan syndrome, aged 26.6±2.3 years old, with BMI 20.5±1.03Kg/m2 and 22 healthy individuals matched for gender, age (26.4±0.78 years old, p=NS) and BMI (22.4±0.86 Kg/m2). Arterial stiffness was evaluated by measuring carotid-femoral pulse wave velocity (PWV), while augmentation pressure and augmentation index (AIx) were also determined, as measures of arterial wave reflections. Endothelial function was evaluated by determining flow mediated dilation (FMD) in the brachial artery while matrix metalloproteinase 9 (MMP-9) levels were determined by ELISA. Results: Patients with Marfan syndrome had significantly lower pulse pressure in the radial artery (41.0±1.07mmHg) compared to controls (51.3±4.4mmHg). In addition, patients had higher AIx (17.6±2.4%) and augmentation pressure (5.44±0.65mmHg) compared to controls (7.72±3.43% and 2.41±1.14mmHg respectively, p<0.05 for both). However, the difference in PWV between patients and controls did not reach statistical significance (6.33±0.33 vs 5.96±0.23m/s respectively, p=NS). Patients with Marfan syndrome had lower FMD (2.05±1.13%) and higher plasma MMP-9 (827±70ng/ml) compared to controls (6.8±2.3% p<0.05 and 326±50ng/ml, p<0.01). Conclusions: Marfan syndrome is associated with increased MMP-9 levels, as well as with elevated augmentation index and augmentation pressure compared to healthy individuals, matched for age, gender and body mass index. Moreover, flow-mediated dilation is also impaired in these subjects. These findings suggest that Marfan syndrome directly affects the elastic properties and endothelial function of the arterial tree, with matrix metalloproteinases being important mediators in the pathophysiology of this syndrome.

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Effects of clopidogrel vs. prasugrel vs. ticagrelor on endothelial function, inflammatory parameters, and platelet function in patients with acute coronary syndrome undergoing coronary artery stenting: a randomized, blinded, parallel study

European Heart Journal ◽

10.1093/eurheartj/ehz917 ◽

2020 ◽

Vol 41 (33) ◽

pp. 3144-3152 ◽

Cited By ~ 12

Author(s):

Boris Schnorbus ◽

Andreas Daiber ◽

Kerstin Jurk ◽

Silke Warnke ◽

Jochem Koenig ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Endothelial Function ◽

Adenosine Diphosphate ◽

Platelet Inhibition ◽

Clinical Parameter ◽

Mean Difference ◽

Low Flow ◽

Flow Mediated Dilation ◽

Coronary Syndrome ◽

The Impact

Abstract Aims In a randomized, parallel, blinded study, we investigate the impact of clopidogrel, prasugrel, or ticagrelor on peripheral endothelial function in patients undergoing stenting for an acute coronary syndrome. Methods and results The primary endpoint of the study was the change in endothelium-dependent flow-mediated dilation (FMD) following stenting. A total of 90 patients (age 62 ± 9 years, 81 males, 22 diabetics, 49 non-ST elevation myocardial infarctions) were enrolled. There were no significant differences among groups in any clinical parameter. Acutely before stenting, all three drugs improved FMD without differences between groups (P = 0.73). Stenting blunted FMD in the clopidogrel and ticagrelor group (both P < 0.01), but not in the prasugrel group. During follow-up, prasugrel was superior to clopidogrel [mean difference 2.13, 95% confidence interval (CI) 0.68–3.58; P = 0.0047] and ticagrelor (mean difference 1.57, 95% CI 0.31–2.83; P = 0.0155), but this difference was limited to patients who received the study therapy 2 h before stenting. Ticagrelor was not significantly superior to clopidogrel (mean difference 0.55, 95% CI −0.73 to 1.82; P = 0.39). No significant differences were seen among groups for low-flow-mediated dilation. Plasma interleukin (IL)-6 (P = 0.02 and P = 0.01, respectively) and platelet aggregation reactivity in response to adenosine diphosphate (P = 0.002 and P = 0.035) were lower in the prasugrel compared to clopidogrel and ticagrelor group. Conclusion As compared to ticagrelor and clopidogrel, therapy with prasugrel in patients undergoing stenting for an acute coronary syndrome is associated with improved endothelial function, stronger platelet inhibition, and reduced IL-6 levels, all of which may have prognostic implications. This effect was lost in patients who received the study medication immediately after stenting. EUDRACT-No 2011-005305-73

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Vitamin D Receptor Activation Mitigates the Impact of Uremia on Endothelial Function in the 5/6 Nephrectomized Rats

International Journal of Endocrinology ◽

10.1155/2010/625852 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 28

Author(s):

J. Ruth Wu-Wong ◽

William Noonan ◽

Masaki Nakane ◽

Kristin A. Brooks ◽

Jason A. Segreti ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Heart Rate ◽

Vitamin D ◽

Endothelial Function ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Receptor Activation ◽

The Impact

Endothelial dysfunction increases cardiovascular disease risk in chronic kidney disease (CKD). This study investigates whether VDR activation affects endothelial function in CKD. The 5/6 nephrectomized (NX) rats with experimental chronic renal insufficiency were treated with or without paricalcitol, a VDR activator. Thoracic aortic rings were precontracted with phenylephrine and then treated with acetylcholine or sodium nitroprusside. Uremia significantly affected aortic relaxation (% in NX rats versus % in SHAM at 30 M acetylcholine). The endothelial-dependent relaxation was improved to –%, –%, and –% in NX rats treated with paricalcitol at 0.021, 0.042, and 0.083 g/kg for two weeks, respectively, while paricalcitol at 0.042 g/kg did not affect blood pressure and heart rate. Parathyroid hormone (PTH) suppression alone did not improve endothelial function since cinacalcet suppressed PTH without affecting endothelial-dependent vasorelaxation. N-omega-nitro-L-arginine methyl ester completely abolished the effect of paricalcitol on improving endothelial function. These results demonstrate that VDR activation improves endothelial function in CKD.

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