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1.
Int J Cardiol ; 268: 125-131, 2018 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-29861102

RESUMEN

BACKGROUND: Interventional closure of left atrial appendage (LAAC) represents an alternative for stroke prevention in patients with non-valvular atrial fibrillation. Whether LAAC may affect metabolomic pathways has not been investigated yet. This study evaluates the impact of LAAC on the metabolism of essential amino acids, kynurenine and creatinine. METHODS: Peripheral blood samples of prospectively enrolled patients undergoing successful LAAC were taken before (T0) and 6 months after (T1, mid-term follow-up). Targeted metabolomic profiling was performed using electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and MS/MS measurements focusing on metabolism of essential amino acids. RESULTS: 44 patients with non-valvular AF (mean CHA2DS2-VASc score 4, mean HAS-BLED score 4) were enrolled. Changes in metabolites of essential amino acids, myocardial contraction and bioenergetic efficacy, such as phenylalanine (percentage change 8.2%, p = 0.006), tryptophan (percentage change 20.3%, p = 0.0006), tyrosine (percentage change 20.2%, p = 0.0001), creatinine (percentage change 7.2%, p > 0.05) and kynurenine (percentage change 8.3%, p = 0.0239) were found at mid-term follow-up. CONCLUSIONS: LAAC may affect the metabolism of essential amino acids and bioenergetic efficacy. ClinicalTrials.gov Identifier: NCT02985463.


Asunto(s)
Aminoácidos Esenciales/sangre , Apéndice Atrial/metabolismo , Apéndice Atrial/cirugía , Metabolismo Energético/fisiología , Metabolómica/métodos , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Espectrometría de Masa por Ionización de Electrospray/métodos , Resultado del Tratamiento , Dispositivos de Cierre Vascular
2.
Sci Rep ; 8(1): 5894, 2018 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-29650978

RESUMEN

Patients with non-valvular atrial fibrillation (AF) and a high risk for oral anticoagulation can be treated by percutaneous implantation of left atrial appendage occlusion devices (LAAC) to reduce the risk of cardio-embolic stroke. This study evaluates whether LAAC may influence lipid metabolism, which has never been investigated before. Patients with successful LAAC were included consecutively. Venous peripheral blood samples of patients were collected immediately before (T0, baseline) and 6 months after (T1, mid-term) LAAC. A targeted metabolomics approach based on electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and MS/MS measurements was performed. A total of 34 lipids revealed a significant change from baseline to mid-term follow-up after successful LAAC. Subgroup analysis revealed confounding influence by gender, age, diabetes mellitus type II, body mass index, left ventricular ejection fraction, creatinine and NT-proBNP. After multivariable adjustment within logistic regression models, these 34 lipids were still significantly altered after LAAC. Successful percutaneous LAAC may affect lipid metabolism and thereby may potentially affect pro-atherogenic and cardio-toxic effects.


Asunto(s)
Apéndice Atrial/metabolismo , Fibrilación Atrial/sangre , Diabetes Mellitus Tipo 2/sangre , Lípidos/sangre , Metaboloma , Intervención Coronaria Percutánea/métodos , Factores de Edad , Anciano , Anciano de 80 o más Años , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/cirugía , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Índice de Masa Corporal , Creatinina/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Diabetes Mellitus Tipo 2/cirugía , Ecocardiografía Transesofágica , Femenino , Humanos , Metabolismo de los Lípidos , Lípidos/clasificación , Modelos Logísticos , Masculino , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales , Espectrometría de Masa por Ionización de Electrospray , Volumen Sistólico/fisiología , Espectrometría de Masas en Tándem
3.
Metabolomics ; 14(2): 20, 2018 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-30830322

RESUMEN

The article Occlusion of left atrial appendage aff ects metabolomic profile:focus on glycolysis, tricarboxylic acid and urea metabolism, written by K. Sattler, M. Behnes, C. Barth, A. Wenke, B. Sartorius, I. El-Battrawy, K. Mashayekhi, J. Kuschyk, U. Hoffmann, T. Papavasiliu, C. Fastner, S. Baumann, S. Lang, X. Zhou, G. Yücel, M. BorggrefeI, Akin, was originally published Online First without open access.

4.
Herz ; 42(2): 138-150, 2017 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-28229199

RESUMEN

Coronary artery disease (CAD) represents a common structural cause for developing cardiac arrest in older patients, whereas in young adults cardiac arrest is more often caused by cardiomyopathies and cardiac channelopathies. A structural heart disease is known in almost 50% of patients prior to cardiac arrest. The present review outlines current interventional and operative therapeutic options for patients surviving cardiac arrest. The focus is on associations between epidemiological data on the incidence of malignant arrhythmias causing cardiac arrest depending on the presence or absence of CAD. Furthermore, the potential benefits of an early coronary revascularization as well as of a prompt complete coronary revascularization compared to the individual treatment of the so-called culprit lesion only are described. Finally, the advantages of invasive therapies for patients surviving cardiac arrest, such as targeted temperature management and mechanical cardiac assist devices, are elucidated. Cardiac assist devices comprise the use of the intra-aortic balloon pump (IABP) and devices for extracorporeal life support (ECLS) for peripheral and central support of the right and left heart chambers.


Asunto(s)
Arritmias Cardíacas/mortalidad , Arritmias Cardíacas/prevención & control , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/terapia , Muerte Súbita Cardíaca/prevención & control , Corazón Auxiliar/estadística & datos numéricos , Revascularización Miocárdica/mortalidad , Muerte Súbita Cardíaca/epidemiología , Medicina Basada en la Evidencia , Humanos , Revascularización Miocárdica/estadística & datos numéricos , Prevalencia , Recurrencia , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento
5.
Metabolomics ; 13(11): 127, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29391863

RESUMEN

BACKGROUND: Left atrial appendage (LAA) closure (LAAC) by implantation of an occlusion device is an established cardiac intervention to reduce risk of stroke while avoiding intake of oral anticoagulation medication during atrial fibrillation. Cardiac interventions can alter local or systemic gene and protein expression. Effects of LAAC on systemic metabolism have not been studied yet. OBJECTIVES: We aimed to study the effects of interventional LAAC on systemic metabolism. METHODS: Products of glycolysis, tricarboxylic acid and urea metabolism were analyzed by ESI-LC-MS/MS and MS/MS using the AbsoluteIDQ™ p180 Kit in plasma of 44 patients undergoing successful interventional LAAC at baseline (T0) and after 6 months (T1). RESULTS: During follow up, plasma concentrations of several parameters of glycolysis and tricarboxylic acid cycle (TCA) and urea metabolism increased (alanine, hexose, proline, sarcosine), while others decreased (aspartate, glycine, SDMA, serine). Multivariate linear regression analysis showed that time after interventional LAAC was an independent predictor for metabolite changes, including the decrease of SDMA (beta -0.19, p < 0.01) and the increase of sarcosine (beta 0.16, p < 0.01). CONCLUSIONS: Successful interventional LAAC affects different pathways of the metabolome, which are probably related to cardiac remodeling. The underlying mechanisms as well as the long term effects have to be studied in the future.

6.
Herz ; 41(7): 585-590, 2016 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-27484494

RESUMEN

Chronic occlusion of coronary arteries also known as chronic total occlusions (CTO) are found in approximately 20 % of patients undergoing percutaneous coronary interventions (PCI) and in approximately 50 % of patients after coronary artery bypass grafts (CABG). As a result of technical advancements in retrograde recanalization techniques specialized centers can now achieve success rates of over 85 %, regardless of the CTO anatomy. Given the complexity of retrograde CTO techniques, a consensus paper issued by the Euro CTO Club requires interventional cardiologists to have sufficient experience in antegrade approaches (>300 antegrade CTO cases and >50 per year) with an additional training program (25 retrograde cases each as first and second operating surgeon) before becoming a qualified independent retrograde surgeon. The increased investment in time and technical resources can only be justified if the patient has a clear clinical benefit. This technical advancement and the progressively clearer evidence that complete revascularization can be achieved in patients with multivessel coronary artery disease have attracted growing interest in recent years from interventional cardiologists in the recanalization of CTO.


Asunto(s)
Prótesis Vascular/normas , Estenosis Coronaria/diagnóstico , Estenosis Coronaria/cirugía , Revascularización Miocárdica/normas , Intervención Coronaria Percutánea/normas , Guías de Práctica Clínica como Asunto , Cardiología/normas , Enfermedad Crónica , Alemania , Humanos , Revascularización Miocárdica/instrumentación , Revascularización Miocárdica/métodos , Stents/normas
7.
Reprod Fertil Dev ; 28(6): 776-84, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25455885

RESUMEN

The efficiency of various assisted reproductive techniques can be improved by preconditioning the gametes and embryos with sublethal hydrostatic pressure treatment. However, the underlying molecular mechanism responsible for this protective effect remains unknown and requires further investigation. Here, we studied the effect of optimised hydrostatic pressure treatment on the global gene expression of mouse oocytes after embryonic genome activation. Based on a gene expression microarray analysis, a significant effect of treatment was observed in 4-cell embryos derived from treated oocytes, revealing a transcriptional footprint of hydrostatic pressure-affected genes. Functional analysis identified numerous genes involved in protein synthesis that were downregulated in 4-cell embryos in response to hydrostatic pressure treatment, suggesting that regulation of translation has a major role in optimised hydrostatic pressure-induced stress tolerance. We present a comprehensive microarray analysis and further delineate a potential mechanism responsible for the protective effect of hydrostatic pressure treatment.


Asunto(s)
Blastocisto/metabolismo , Regulación hacia Abajo , Ectogénesis , Embrión de Mamíferos/metabolismo , Oocitos/metabolismo , Proteínas Ribosómicas/metabolismo , Estrés Fisiológico , Animales , Animales no Consanguíneos , Blastocisto/citología , Blastocisto/enzimología , Técnicas de Cultivo de Embriones , Embrión de Mamíferos/citología , Embrión de Mamíferos/enzimología , Femenino , Perfilación de la Expresión Génica , Presión Hidrostática/efectos adversos , Masculino , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Oocitos/citología , Oocitos/enzimología , Biosíntesis de Proteínas , ARN Mensajero/metabolismo , Proteínas Ribosómicas/genética , Organismos Libres de Patógenos Específicos , Inyecciones de Esperma Intracitoplasmáticas
8.
Biomaterials ; 35(6): 2001-10, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24331702

RESUMEN

The complex pathophysiology of chronic ulceration in diabetic patients is poorly understood; diabetes-related lower limb amputation is a major health issue, which has limited effective treatment regimes in the clinic. This study attempted to understand the complex pathology of hyperglycemic wound healing by showing profound changes in gene expression profiles in wounded human keratinocytes in hyperglycemic conditions compared to normal glucose conditions. In the hyper-secretory wound microenvironment of hyperglycemia, Rab18, a secretory control molecule, was found to be significantly downregulated. Using a biomaterial platform for dual therapy targeting the two distinct pathways, this study aimed to resolve the major dysregulated pathways in hyperglycemic wound healing. To complement Rab18, and promote angiogenesis eNOS was also targeted, and this novel Rab18-eNOS therapy via a dynamically controlled 'fibrin-in-fibrin' delivery system, demonstrated enhanced wound closure, by increasing functional angiogenesis and reducing inflammation, in an alloxan-induced hyperglycemic preclinical ear ulcer model of compromised wound healing.


Asunto(s)
Fibrina/química , Hiperglucemia/tratamiento farmacológico , Cicatrización de Heridas/fisiología , Animales , Proliferación Celular/efectos de los fármacos , Humanos , Hiperglucemia/metabolismo , Inmunohistoquímica , Inflamación/metabolismo , Queratinocitos/citología , Queratinocitos/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo III/metabolismo , Conejos , Proteínas de Unión al GTP rab/metabolismo
9.
Atherosclerosis ; 221(2): 325-32, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22381691

RESUMEN

OBJECTIVE: The most common cause of death in diabetes mellitus is cardiovascular disease. Patients frequently undergo vascular intervention such as stenting. The occurrence of in stent restenosis (ISR) has been reduced by the use of drug eluting stents in non-diabetic patients but the incidence of restenosis and stent thrombosis remains higher in diabetic patients. We investigated the pathogenesis of in stent restenosis in an animal model of type 2 diabetes mellitus. METHODS AND RESULTS: Stents were placed in Zucker Fatty rat (ZFR) and wild type rat carotid arteries, and tissues were harvested 14 days post surgery for morphometric analysis. Unstented carotid arteries from both groups were harvested for microarray analysis. In vitro apoptosis, proliferation and migration assays were performed on rat and human aortic endothelial cells (EC). ZFRs developed an exaggerated intimal response to stent placement compared to wild type controls 14 days post stent placement. MRP8 and MRP14 were up-regulated in unstented ZFR carotid arteries in comparison to controls. Expression of MRP8/14 was also elevated in EC exposed to high glucose conditions. EC function was impaired by high glucose concentrations, and this effect could be mimicked by MRP8 over-expression. MRP8 knockdown by shRNA significantly restored EC function after exposure to high glucose concentrations. MRP8 expression in glucose exposed cells was also inhibited using pharmacological blockade of glucose-induced pathways. CONCLUSIONS: EC dysfunction caused by elevated glucose levels could be mimicked by MRP8/14 over-expression and reversed/prevented by MRP8 knockdown. Thus, MRP8/14 likely plays a role in exaggerated ISR in diabetes mellitus, and MRP8 inhibition may be useful in improving outcome after stent placement in diabetes mellitus.


Asunto(s)
Angioplastia/efectos adversos , Angioplastia/instrumentación , Calgranulina A/metabolismo , Arterias Carótidas/metabolismo , Estenosis Carotídea/etiología , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/etiología , Neointima/etiología , Stents , Animales , Apoptosis , Glucemia/metabolismo , Calgranulina A/genética , Calgranulina B/genética , Calgranulina B/metabolismo , Arterias Carótidas/patología , Estenosis Carotídea/genética , Estenosis Carotídea/metabolismo , Estenosis Carotídea/patología , Movimiento Celular , Proliferación Celular , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/genética , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/patología , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Células Endoteliales/patología , Perfilación de la Expresión Génica/métodos , Células HEK293 , Células HeLa , Humanos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Neointima/genética , Neointima/metabolismo , Neointima/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Interferencia de ARN , Ratas , Ratas Zucker , Transfección
10.
Cell Transplant ; 21(6): 1095-107, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22304991

RESUMEN

Tissue necrosis resulting from critical limb ischemia (CLI) leads to amputation in a significant number of patients. Autologous cell therapy using angiogenic cells such as endothelial progenitor cells (EPCs) holds promise as a treatment for CLI but a limitation of this treatment is that the underlying disease etiology that resulted in CLI may also contribute to dysfunction of the therapeutic EPCs. This study aimed to elucidate the mechanism of EPC dysfunction using diabetes mellitus as a model and to determine whether correction of this defect in dysfunctional EPCs ex vivo would improve the outcome after cell transplantation in the murine hind limb ischemia model. EPC dysfunction was confirmed in a homogenous population of patients with type 1 diabetes mellitus and a microarray study was preformed to identify dysregulated genes. Notably, the secreted proangiogenic protein osteopontin (OPN) was significantly downregulated in diabetic EPCs. Furthermore, OPN-deficient mice showed impaired recovery following hind limb ischemia, suggesting a critical role for OPN in postnatal neovascularization. EPCs isolated from OPN KO mice showed decreased ability to adhere to endothelial cells as well as impaired angiogenic potential. However, this dysfunction was reversed upon exposure to recombinant OPN, suggesting that OPN may act in an autocrine manner on EPCs. Indeed, exposure of OPN knockout (KO) EPCs to OPN was sufficient to induce the secretion of angiogenic proteins (IL-6, TGF-α, and FGF-α). We also demonstrated that vascular regeneration following hind limb ischemia in OPN KO mice was significantly improved upon injection of EPCs preexposed to OPN. We concluded that OPN acts in an autocrine manner on EPCs to induce the secretion of angiogenic proteins, thereby playing a critical role in EPC-mediated neovascularization. Modification of cells by exposure to OPN may improve the efficacy of autologous EPC transplantation via the enhanced secretion of angiogenic proteins.


Asunto(s)
Células Endoteliales/citología , Osteopontina/farmacología , Enfermedades Vasculares Periféricas/terapia , Células Madre/efectos de los fármacos , Adulto , Animales , Tratamiento Basado en Trasplante de Células y Tejidos , Células Cultivadas , Diabetes Mellitus Tipo 1/patología , Femenino , Factores de Crecimiento de Fibroblastos/metabolismo , Miembro Posterior/irrigación sanguínea , Células Endoteliales de la Vena Umbilical Humana , Humanos , Interleucina-6/metabolismo , Isquemia/metabolismo , Isquemia/terapia , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neovascularización Fisiológica/efectos de los fármacos , Osteopontina/genética , Osteopontina/metabolismo , Enfermedades Vasculares Periféricas/metabolismo , Conejos , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacología , Regeneración , Trasplante de Células Madre , Células Madre/citología , Células Madre/metabolismo , Factor de Crecimiento Transformador alfa/metabolismo , Adulto Joven
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