RESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary disorders, characterized by the formation of multiple cysts in the kidneys and other organs, as well as noncystic manifestations such as cerebral aneurysm. The most common cardiovascular disorders associated with ADPKD include valvular abnormalities and aortic aneurysm. An association between ADPKD and impaired left ventricular function has occasionally been reported. We describe a 74-year-old woman with ADPKD and exertional dyspnea. Impaired left ventricular function resulting from noncompaction of the ventricular myocardium (NVM) and secondary left ventricular aneurysm were diagnosed. Cardiac sarcoidosis and ischemic heart disease were ruled out. Myocardial ischemia resulting from NVM was the presumptive cause of the ventricular aneurysm. To our knowledge, this is the first report of concurrent isolated NVM and left ventricular aneurysm in a patient with ADPKD. ADPKD and various cardiomyopathies, including NVM, are all reported to involve mutations of sarcomere genes, suggesting a possible link between the conditions.
Asunto(s)
No Compactación Aislada del Miocardio Ventricular/etiología , Riñón Poliquístico Autosómico Dominante/complicaciones , Anciano , Femenino , Humanos , No Compactación Aislada del Miocardio Ventricular/diagnósticoRESUMEN
Left ventricular (LV) apical thrombus can rarely occur during the early phase of takotsubo cardiomyopathy. We report such a case that was depicted clearly in contrast computed tomography (CT) but not in initial echocardiography. Because LV thrombus may lead to thromboembolic events, we should evaluate all patients with takotsubo cardiomyopathy for the presence of a LV thrombus. LV thrombus is generally recognized with echocardiography in the course of follow-up, but limited depiction of the LV apex with echocardiography can make evaluation of LV thrombus difficult. Contrast CT is useful to detect LV apical thrombus associated with takotsubo cardiomyopathy.
Asunto(s)
Medios de Contraste/administración & dosificación , Ventrículos Cardíacos/diagnóstico por imagen , Cardiomiopatía de Takotsubo/complicaciones , Trombosis/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anticoagulantes/uso terapéutico , Angiografía Coronaria , Ecocardiografía Doppler , Electrocardiografía , Femenino , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Cardiomiopatía de Takotsubo/diagnóstico por imagen , Cardiomiopatía de Takotsubo/fisiopatología , Trombosis/tratamiento farmacológico , Trombosis/etiología , Resultado del TratamientoRESUMEN
Thrombotic microangiopathy (TMA) is a rare but lethal multisystem disease characterized by peripheral thrombocytopenia, microangiopathic hemolytic anemia, fever, and various stages of renal and neurological dysfunctions.(1,2)) The causes of TMA are mainly thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS), and cases of TMA related to myelodysplastic syndrome (MDS) are quite rare. Herein, we report a case of acute myocardial infarction (AMI) caused by TMA which is strongly suspected to have a relationship to MDS, and discuss the treatment of our patient who needed antiplatelet or anticoagulant therapy after AMI, while on the other hand, had pancytopenia and a bleeding event due to MDS.
Asunto(s)
Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/diagnóstico , Infarto del Miocardio/etiología , Microangiopatías Trombóticas/complicaciones , Microangiopatías Trombóticas/diagnóstico , Anciano , Humanos , Masculino , Infarto del Miocardio/diagnóstico por imagenAsunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Angioplastia por Láser/métodos , Reestenosis Coronaria/terapia , Estenosis Coronaria/terapia , Anciano , Angioplastia Coronaria con Balón/métodos , Estudios de Cohortes , Angiografía Coronaria/métodos , Reestenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/diagnóstico por imagen , Stents Liberadores de Fármacos , Femenino , Estudios de Seguimiento , Humanos , Japón , Láseres de Excímeros/uso terapéutico , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Falla de Prótesis , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Adrenomedullin (AM) is a novel vasodilating peptide involved in the regulation of circulatory homeostasis and implicated in the pathophysiology of cardiovascular disease. We tested the hypothesis that AM also possesses angiogenic properties. Using laser Doppler perfusion imaging, we found that AM stimulated recovery of blood flow to the affected limb in the mouse hind-limb ischemia model. AM exerted this effect in part by promoting expression of vascular endothelial growth factor (VEGF) in the ischemic limb, and immunostaining for CD31 showed the enhanced flow to reflect increased collateral capillary density. By enhancing tumor angiogenesis, AM also promoted the growth of subcutaneously transplanted sarcoma 180 tumor cells. However, heterozygotic AM knockout mice (AM+/-) showed significantly less blood flow recovery with less collateral capillary development and VEGF expression than their wild-type littermates. Similarly, mice treated with AM22-52, a competitive inhibitor of AM, showed reduced capillary development, and growth of sarcoma 180 tumors was inhibited in AM+/- and AM22-52-treated mice. Notably, administration of VEGF or AM rescued blood flow recovery and capillary formation in AM+/- and AM22-52-treated mice. In cocultures of endothelial cells and fibroblasts, AM enhanced VEGF-induced capillary formation, whereas in cultures of endothelial cells AM enhanced VEGF-induced Akt activation. These results show that AM possesses novel angiogenic properties mediated by its ability to enhance VEGF expression and Akt activity. This may make AM a useful therapeutic tool for relieving ischemia; conversely, inhibitors of AM could be useful for clinical management of tumor growth.
Asunto(s)
Terapia Genética , Miembro Posterior/irrigación sanguínea , Isquemia/terapia , Neovascularización Patológica/inducido químicamente , Neovascularización Fisiológica/efectos de los fármacos , Péptidos/farmacología , Adrenomedulina , Animales , Capilares/efectos de los fármacos , Técnicas de Cocultivo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/enzimología , Células Endoteliales/metabolismo , Endotelio Vascular/citología , Activación Enzimática/efectos de los fármacos , Fibroblastos/citología , Humanos , Inyecciones Intramusculares , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Ratones Noqueados , Fragmentos de Péptidos/uso terapéutico , Fragmentos de Péptidos/toxicidad , Péptidos/antagonistas & inhibidores , Péptidos/deficiencia , Péptidos/uso terapéutico , Péptidos/toxicidad , Fosforilación/efectos de los fármacos , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Distribución Aleatoria , Proteínas Recombinantes de Fusión/fisiología , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Sarcoma 180/irrigación sanguínea , Sarcoma 180/tratamiento farmacológico , Carga Tumoral/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/toxicidadAsunto(s)
Antibióticos Antineoplásicos/efectos adversos , Antineoplásicos Fitogénicos/efectos adversos , Doxorrubicina/efectos adversos , Pruebas de Función Hepática/normas , Linfoma/tratamiento farmacológico , Vincristina/efectos adversos , Anciano de 80 o más Años , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Biomarcadores/sangre , Resultado Fatal , Humanos , Hígado/patología , Hepatopatías/metabolismo , Linfoma/complicaciones , Masculino , Tasa de Depuración Metabólica , Valor Predictivo de las PruebasRESUMEN
OBJECTIVES: Neoendothelialization by circulating endothelial progenitor cells has been a topic of recent research. The extent and scale of this process in humans is not well understood. We examined the extent of neoendothelialization of the aorta and peripheral arteries in the case of a patient who underwent peripheral blood stem cell transplantation for acute radiation syndrome. METHODS: Human tissue samples from the aorta and peripheral arteries were obtained at autopsy. Endothelial cells were isolated, confirmed by von Willebrand factor immunostaining, and then subjected to fluorescent in situ hybridization analysis using X- and Y-chromosome specific probes to examine neoendothelialization by donor cells as possible in this case in which the donor and recipient were of different genders. RESULTS: The aorta showed almost 25% of all endothelial cells to be replaced by donor-origin endothelial cells. The peripheral arteries were also replaced but to a lesser extent. DISCUSSION: The present study provides evidence that peripheral blood is a source of endothelial progenitor cells in humans. Neoendothelialization of the aorta occurs to a significant extent under certain conditions suggesting the potential for exploitation of therapeutic neovascularization by transplantation of circulating endothelial progenitor cells.
Asunto(s)
Endotelio Vascular/patología , Reactores Nucleares , Trasplante de Células Madre de Sangre Periférica , Traumatismos por Radiación/cirugía , Liberación de Radiactividad Peligrosa , Adulto , Aorta , Cromosomas Humanos X , Endotelio Vascular/efectos de la radiación , Resultado Fatal , Femenino , Supervivencia de Injerto , Histocitoquímica , Humanos , Hibridación Fluorescente in Situ , Masculino , Neovascularización Fisiológica , Traumatismos por Radiación/patología , Donantes de TejidosRESUMEN
OBJECTIVES: To examine the diagnostic performance of circulating oxidized low density lipoprotein levels as a biochemical risk marker of coronary heart disease. DESIGN AND METHODS: 361 patients with coronary artery disease and 710 healthy volunteers as normal controls were examined. Receiver-operating characteristics curve analysis in addition to statistical analysis (univariate, multivariate) were done to determine the usefulness of the assay. RESULTS: Patients with coronary artery disease showed significantly elevated circulating oxidized low density lipoprotein levels. Males less than 70 years of age showed a significant association between oxidized low density lipoprotein levels and coronary artery disease. Receiver-operating characteristics curve analysis showed superior performance (e.g., sensitivity, specificity) of oxidized low density lipoprotein as a diagnostic marker of coronary artery disease as compared against other lipid markers (total cholesterol, triglyceride, high density lipoprotein, lipoprotein (a), and total cholesterol to high density lipoprotein ratio) with optimal performance in younger males. CONCLUSIONS: Oxidized low density lipoprotein levels may be a promising biochemical risk marker of atherosclerotic disease, especially in young males.
Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Lipoproteínas LDL/sangre , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Análisis de Regresión , Factores de Riesgo , Sensibilidad y Especificidad , Estadísticas no ParamétricasAsunto(s)
Bloqueo Atrioventricular/complicaciones , Bloqueo Atrioventricular/diagnóstico , Cardiomiopatía de Takotsubo/complicaciones , Cardiomiopatía de Takotsubo/diagnóstico , Torsades de Pointes/complicaciones , Torsades de Pointes/diagnóstico , Anciano , Bloqueo Atrioventricular/fisiopatología , Electrocardiografía/métodos , Femenino , Humanos , Cardiomiopatía de Takotsubo/fisiopatología , Torsades de Pointes/fisiopatologíaAsunto(s)
Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/etiología , Asma Inducida por Aspirina/complicaciones , Asma Inducida por Aspirina/diagnóstico , Síndrome Coronario Agudo/fisiopatología , Asma Inducida por Aspirina/fisiopatología , Electrocardiografía/métodos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Advanced age is a major risk factor of peripheral artery disease. We examined the effects of the aging-suppressor gene klotho on angiogenesis in response to ischemia by introducing ischemic hindlimb model in mice heterozygously deficient for the klotho gene and in wild type mice. Blood flow recovery as assessed by laser doppler perfusion imaging and angiogenesis as assessed by density of PECAM-1/CD31-positive positive capillaries were markedly impaired in mice heterozygously deficient for the klotho gene (both <0.05). Our findings show that the aging-suppressor gene klotho affects angiogenesis and the possibility that age-related impairment of angiogenesis might be regulated by the klotho gene. Our results present a new possibility of therapeutic angiogenesis for patients of advanced age.
Asunto(s)
Envejecimiento/genética , Proteínas de la Membrana/genética , Neovascularización Fisiológica/genética , Animales , Genes Supresores , Glucuronidasa , Heterocigoto , Isquemia/genética , Proteínas Klotho , Masculino , Proteínas de la Membrana/deficiencia , Ratones , Ratones Noqueados , Factores de TiempoRESUMEN
The klotho gene, originally identified by insertional mutagenesis in mice, suppresses the expression of multiple aging-associated phenotypes. This gene is predominantly expressed in the kidney. Recent studies have shown that expression of renal klotho gene is regulated in animal models of metabolic diseases and in humans with chronic renal failure. However, little is known about the mechanisms and the physiological relevance of the regulation of the expression of the klotho gene in the kidney in some diseased conditions. In the present study, we first investigated the role of angiotensin II in the regulation of renal klotho gene expression. Long-term infusion of angiotensin II downregulated renal klotho gene expression at both the mRNA and protein levels. This angiotensin II-induced renal klotho downregulation was an angiotensin type 1 receptor-dependent but pressor-independent event. Adenovirus harboring mouse klotho gene (ad-klotho, 3.3x10(10) plaque forming units) was also intravenously administered immediately before starting angiotensin II infusion in some rats. This resulted in a robust induction of Klotho protein in the liver at day 4, which was still detectable 14 days after the gene transfer. Ad-klotho gene transfer, but not ad-lacZ gene transfer, caused an improvement of creatinine clearance, decrease in urinary protein excretion, and amelioration of histologically demonstrated tubulointerstitial damage induced by angiotensin II administration. Our data suggest that downregulation of the renal klotho gene may have an aggravative role in the development of renal damage induced by angiotensin II, and that induction of the klotho gene may have therapeutic possibilities in treating angiotensin II-induced end organ damage.