Reactive Vasodilation Predicts Mortality in Primary Systemic Light-Chain Amyloidosis

Stamatelopoulos, Kimon; Georgiopoulos, Georgios; Athanasouli, Fani; Νικολάου, Παναγιώτα; Lykka, Marita; Ρούσσου, Μαρία; Gavriatopoulou, Maria; Laina, Ageliki; Trakada, Georgia; Charakida, Marietta; Stamatelopoulos, Kimon; Petropoulos, Ioannis N.; Pamboukas, Constantinos; Karakitsou, Marina; Papamichael, Christos; Gatsiou, Aikaterini; Lambrinoudaki, Ιrene; Terpos, Evangelos; Stellos, Konstantinos; Andreadou, Ioanna; Dimopoulos, Meletios A.

doi:10.1161/circresaha.119.314862

Cited by 26 publications

(22 citation statements)

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“…To further investigate the endothelial homeostasis as well as the redox status of the carfilzomib- and metformin-treated mice, the total circulating nitrates/nitrites (NO x ) content in the sera as a biomarker of NO release, 3-nitrotyrosine (3-NT), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 ( nox2 ) and NADPH oxidase 4 ( nox4 ) redox-related genes in the aortic tissues as markers of nitro-oxidative stress were assessed [ 12 ]. Neither carfilzomib nor metformin or the drugs coadministration led to any significant changes in NO x and 3-NT content ( Figure 4 A,B), whereas nox2 and nox4 levels did not differ among groups ( Figure 4 C).…”

Section: Resultsmentioning

confidence: 99%

“…For serum nitrates-nitrites (NO x ) measurements, sera were concentrated using 10 kDa cut-off filters and flow-through sample was further analyzed accordingly to the manufacturer’s instructions using a commercially available kit (No. 780001, Cayman Chemicals) [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

“…Subsequently samples were centrifuged at 5000× g for 15 min and lysate was further analyzed using a commercially available ELISA kit, accordingly the manufacturer’s instructions (3-nitrotyrosine ELISA Kit: No. K4158-100; BioVision) [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

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Investigating the Vascular Toxicity Outcomes of the Irreversible Proteasome Inhibitor Carfilzomib

Efentakis

Doerschmann

Witzler

et al. 2020

IJMS

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Background: Carfilzomib’s (Cfz) adverse events in myeloma patients include cardiovascular toxicity. Since carfilzomib’s vascular effects are elusive, we investigated the vascular outcomes of carfilzomib and metformin (Met) coadministration. Methods: Mice received: (i) saline; (ii) Cfz; (iii) Met; (iv) Cfz+Met for two consecutive (acute) or six alternate days (subacute protocol). Leucocyte-derived reactive oxygen species (ROS) and serum NOx levels were determined and aortas underwent vascular and molecular analyses. Mechanistic experiments were recapitulated in aged mice who received similar treatment to young animals. Primary murine (prmVSMCs) and aged human aortic smooth muscle cells (HAoSMCs) underwent Cfz, Met and Cfz+Met treatment and viability, metabolic flux and p53-LC3-B expression were measured. Experiments were recapitulated in AngII, CoCl2 and high-glucose stimulated HAoSMCs. Results: Acutely, carfilzomib alone led to vascular hypo-contraction and increased ROS release. Subacutely, carfilzomib increased ROS release without vascular manifestations. Cfz+Met increased PGF2α-vasoconstriction and LC3-B-dependent autophagy in both young and aged mice. In vitro, Cfz+Met led to cytotoxicity and autophagy, while Met and Cfz+Met shifted cellular metabolism. Conclusion: Carfilzomib induces a transient vascular impairment and oxidative burst. Cfz+Met increased vascular contractility and synergistically induced autophagy in all settings. Therefore, carfilzomib cannot be accredited for a permanent vascular dysfunction, while Cfz+Met exert vasoprotective potency.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Investigating the Vascular Toxicity Outcomes of the Irreversible Proteasome Inhibitor Carfilzomib

Efentakis

Doerschmann

Witzler

et al. 2020

IJMS

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“…Flow-mediated dilation was assessed using a 7.0 to 14.0 Hz multifrequency linear array probe, attached to a high-resolution ultrasound machine (Vivid 7 Pro; GE) as previously described. 9,11 The right brachial artery was longitudinally imaged above the antecubital fossa in a supinated position of the forearm. A pneumatic cuff was placed around the forearm, and after the initial measurements at resting conditions, the cuff was rapidly inflated to 250 mm Hg for 5 minutes and subsequently deflated.…”

Section: Methodsmentioning

confidence: 99%

Anti-Müllerian Hormone Concentrations Are Inversely Associated With Subclinical Atherosclerosis in Premenopausal Women

et al. 2020

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Anti-Müllerian hormone (AMH), which is secreted by granulosa cells of late preantral and small antral follicles, is a marker of ovarian reserve. The association of ovarian reserve with subclinical atherosclerosis in women of reproductive age is currently unknown. We primary investigated whether AMH levels are associated with markers of subclinical atherosclerosis in healthy, normally menstruating women. In this cross-sectional study, vascular structure and function were assessed by measurement of carotid and femoral intima–media thickness (IMT), flow-mediated dilation, carotid–femoral pulse wave velocity and augmentation index. Lipid profile and serum AMH concentrations were also measured. Seventy premenopausal women, aged 32.7 ± 6.5 years, were included. Mean AMH levels were lower in smokers than in non-smokers and negatively associated with total cholesterol (TC) levels. An inverse association between mean AMH concentrations and femoral and carotid IMT in all segments was observed. No correlation with other markers of subclinical atherosclerosis or established cardiovascular (CV) risk factors was found. After multivariable adjustment, the association between AMH concentrations and combined carotid IMT or carotid bulb IMT remained significant. In conclusion, in healthy, normally ovulating women, AMH concentrations are negatively associated with subclinical atherosclerosis indices and TC levels, independently of established CV risk factors.

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“…Analysis was further adjusted for a prespecified set of confounders, including maternal age, race, parity, weight, height, mean arterial pressure, heart rate and time elapsed from delivery to second visit. To ensure normality of the distribution of dependent variables in linear mixed models, the analysis was repeated after inverse ranking normalization of maternal cardiac markers 15 .…”

Section: Discussionmentioning

confidence: 99%

Maternal cardiac function in gestational diabetes mellitus at 35–36 weeks' gestation and 6 months postpartum

Aguilera

Sierra

Azim

et al. 2020

Ultrasound in Obstet & Gyne

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Objective Women with gestational diabetes mellitus (GDM) are at increased risk for adverse cardiovascular outcome later in life. However, it is uncertain whether this increased risk is due to cardiovascular changes occurring during pregnancy and persisting thereafter or to an adverse underlying cardiovascular risk factor profile. Some studies have reported that GDM is associated with reduced systolic and diastolic left ventricular function in pregnancy; however, it remains unknown whether these changes persist after delivery. The objective of this study was to compare cardiac function and structure in women with GDM and those with uncomplicated pregnancy at 35–36 weeks' gestation and about 6 months after delivery. Methods This was a longitudinal study in which women with GDM and those with uncomplicated pregnancy had detailed cardiovascular assessment at 35–36 weeks' gestation and repeat examination around 6 months after delivery. In all women, left ventricular systolic and diastolic indices were measured and left ventricular mass indexed for body surface area was calculated. Cardiac output and peripheral vascular resistance were also calculated using echocardiography. Linear mixed model analysis accounting for differences in maternal characteristics was carried out to compare findings of cardiovascular function between the GDM group and controls and within each group at 35–36 weeks' gestation and at 6 months after delivery. Results We studied 73 women with GDM and 73 controls with uncomplicated pregnancy. At 35–36 weeks' gestation, women with GDM, compared to controls, had higher E/e′ ratio and lower E/A ratio and global longitudinal systolic strain; there were no significant differences between the groups in ejection fraction. Left ventricular mass indexed for body surface area was also increased in women with GDM. There were no significant differences between the groups in cardiac output and peripheral vascular resistance. At 6 months after delivery, cardiac functional indices improved in both patients with GDM and controls, but in the GDM group, compared to controls, there was a lower degree of improvement in E/A ratio and global longitudinal systolic strain. Conclusion In the third trimester, patients with GDM have subtle differences in diastolic and systolic left ventricular function compared to controls and, despite improvement after delivery, these changes persist for at least 6 months. Long‐term follow‐up is therefore needed to assess whether women with GDM are at risk for an accelerated decline in their cardiac function and, if so, whether this trend can be reversed or delayed by optimal cardiovascular risk factor modification. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

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Reactive Vasodilation Predicts Mortality in Primary Systemic Light-Chain Amyloidosis

Abstract: Supplemental Digital Content is available in the text.

Cited by 26 publications

References 59 publications

Investigating the Vascular Toxicity Outcomes of the Irreversible Proteasome Inhibitor Carfilzomib

Investigating the Vascular Toxicity Outcomes of the Irreversible Proteasome Inhibitor Carfilzomib

Anti-Müllerian Hormone Concentrations Are Inversely Associated With Subclinical Atherosclerosis in Premenopausal Women

Maternal cardiac function in gestational diabetes mellitus at 35–36 weeks' gestation and 6 months postpartum

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