RESUMEN
High-intensity focused ultrasound (HIFU) is a non-invasive method of selective placental vascular occlusion, providing a potential therapy for conditions such as twin-twin transfusion syndrome. In order to translate this technique into human studies, evidence of prolonged fetal recovery and maintenance of a healthy fetal physiology following exposure to HIFU is essential. At 116 ± 2 days gestation, 12 pregnant ewes were assigned to control ( n = 6) or HIFU vascular occlusion ( n = 6) groups and anaesthetized. Placental blood vessels were identified using colour Doppler ultrasound; HIFU-mediated vascular occlusion was performed through intact maternal skin (1.66 MHz, 5 s duration, in situ ISPTA 1.8-3.9 kW cm-2). Unidentifiable colour Doppler signals in targeted vessels following HIFU exposure denoted successful occlusion. Ewes and fetuses were then surgically instrumented with vascular catheters and transonic flow probes and recovered from anaesthesia. A custom-made wireless data acquisition system, which records continuous maternal and fetal cardiovascular data, and daily blood sampling were used to assess wellbeing for 20 days, followed by post-mortem examination. Based on a comparison of pre- and post-treatment colour Doppler imaging, 100% (36/36) of placental vessels were occluded following HIFU, and occlusion persisted for 20 days. All fetuses survived. No differences in maternal or fetal blood pressure, heart rate, heart rate variability, metabolic status or oxygenation were observed between treatment groups. There was evidence of normal fetal maturation and no evidence of chronic fetal stress. There were no maternal injuries and no placental vascular haemorrhage. There was both a uterine and fetal burn, which did not result in any obstetric or fetal complications. This study demonstrates normal long-term recovery of fetal sheep from exposure to HIFU-mediated placental vascular occlusion and underlines the potential of HIFU as a potential non-invasive therapy in human pregnancy.
Asunto(s)
Transfusión Feto-Fetal , Feto , Ultrasonido Enfocado de Alta Intensidad de Ablación , Placenta , Ultrasonografía Doppler , Enfermedades Vasculares , Animales , Femenino , Transfusión Feto-Fetal/diagnóstico por imagen , Transfusión Feto-Fetal/fisiopatología , Transfusión Feto-Fetal/terapia , Feto/diagnóstico por imagen , Feto/fisiopatología , Humanos , Placenta/diagnóstico por imagen , Placenta/fisiopatología , Embarazo , Ovinos , Enfermedades Vasculares/diagnóstico por imagen , Enfermedades Vasculares/embriología , Enfermedades Vasculares/fisiopatología , Enfermedades Vasculares/terapiaRESUMEN
Endothelial cells (ECs) have been found to be capable of acquiring a mesenchymal phenotype through a process known as endothelial-to-mesenchymal transition (EndMT). First seen in the developing embryo, EndMT can be triggered postnatally under certain pathological conditions. During this process, ECs dedifferentiate into mesenchymal stem-like cells (MSCs) and subsequently give rise to cell types belonging to the mesoderm lineage. As EndMT contributes to a multitude of diseases, pharmacological modulation of the signaling pathways underlying EndMT may prove to be effective as a therapeutic treatment. Additionally, EndMT in ECs could also be exploited to acquire multipotent MSCs, which can be readily re-differentiated into various distinct cell types. In this review, we will consider current models of EndMT, how manipulation of this process might improve treatment of clinically important pathologies and how it could be harnessed to advance regenerative medicine and tissue engineering.
Asunto(s)
Embrión de Mamíferos/metabolismo , Células Endoteliales/metabolismo , Células Madre Mesenquimatosas/metabolismo , Mesodermo/metabolismo , Modelos Biológicos , Transducción de Señal , Enfermedades Vasculares/embriología , Animales , Linaje de la Célula , Embrión de Mamíferos/patología , Células Endoteliales/patología , Humanos , Células Madre Mesenquimatosas/patología , Mesodermo/patología , Enfermedades Vasculares/patologíaRESUMEN
Maternal diabetes mellitus is a significant risk factor for structural birth defects, including congenital heart defects and neural tube defects. With the rising prevalence of type 2 diabetes mellitus and obesity in women of childbearing age, diabetes mellitus-induced birth defects have become an increasingly significant public health problem. Maternal diabetes mellitus in vivo and high glucose in vitro induce yolk sac injuries by damaging the morphologic condition of cells and altering the dynamics of organelles. The yolk sac vascular system is the first system to develop during embryogenesis; therefore, it is the most sensitive to hyperglycemia. The consequences of yolk sac injuries include impairment of nutrient transportation because of vasculopathy. Although the functional relationship between yolk sac vasculopathy and structural birth defects has not yet been established, a recent study reveals that the quality of yolk sac vasculature is related inversely to embryonic malformation rates. Studies in animal models have uncovered key molecular intermediates of diabetic yolk sac vasculopathy, which include hypoxia-inducible factor-1α, apoptosis signal-regulating kinase 1, and its inhibitor thioredoxin-1, c-Jun-N-terminal kinases, nitric oxide, and nitric oxide synthase. Yolk sac vasculopathy is also associated with abnormalities in arachidonic acid and myo-inositol. Dietary supplementation with fatty acids that restore lipid levels in the yolk sac lead to a reduction in diabetes mellitus-induced malformations. Although the role of the human yolk in embryogenesis is less extensive than in rodents, nevertheless, human embryonic vasculogenesis is affected negatively by maternal diabetes mellitus. Mechanistic studies have identified potential therapeutic targets for future intervention against yolk sac vasculopathy, birth defects, and other complications associated with diabetic pregnancies.
Asunto(s)
Anomalías Congénitas/embriología , Glucosa/metabolismo , Embarazo en Diabéticas/metabolismo , Enfermedades Vasculares/embriología , Saco Vitelino/embriología , Animales , Ácido Araquidónico/metabolismo , Anomalías Congénitas/metabolismo , Femenino , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Inositol/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , MAP Quinasa Quinasa Quinasa 5/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Embarazo , Tiorredoxinas/metabolismo , Enfermedades Vasculares/metabolismo , Saco Vitelino/irrigación sanguínea , Saco Vitelino/metabolismoRESUMEN
Regional differences in vascular physiology and disease response exist throughout the vascular tree. While these differences in physiology and disease correspond to regional vascular environmental conditions, there is also compelling evidence that the embryonic origins of the smooth muscle inherent to the vessels may play a role. Here, we review what is known regarding the role of embryonic origin of vascular smooth muscle cells during vascular development. The focus of this review is to highlight the heterogeneity in the origins of vascular smooth muscle cells and the resulting regional physiologies of the vessels. Our goal is to stimulate future investigation into this area and provide a better understanding of vascular organogenesis and disease. .
Asunto(s)
Músculo Liso Vascular/embriología , Miocitos del Músculo Liso/metabolismo , Neovascularización Fisiológica , Organogénesis , Enfermedades Vasculares/embriología , Adulto , Animales , Humanos , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Enfermedades Vasculares/patologíaRESUMEN
The majority of severe clinically significant forms of congenital heart disease (CHD) are associated with great artery lesions, including hypoplastic, double, right or interrupted aortic arch morphologies. While fetal and neonatal interventions are advancing, their potential ability to restore cardiac function, optimal timing, location, and intensity required for intervention remain largely unknown. Here, we combine computational fluid dynamics (CFD) simulations with in vivo experiments to test how individual pharyngeal arch artery hemodynamics alter as a result of local interventions obstructing individual arch artery flow. Simulated isolated occlusions within each pharyngeal arch artery were created with image-derived three-dimensional (3D) reconstructions of normal chick pharyngeal arch anatomy at Hamburger-Hamilton (HH) developmental stages HH18 and HH24. Acute flow redistributions were then computed using in vivo measured subject-specific aortic sinus inflow velocity profiles. A kinematic vascular growth-rendering algorithm was then developed and implemented to test the role of changing local wall shear stress patterns in downstream 3D morphogenesis of arch arteries. CFD simulations predicted that altered pressure gradients and flow redistributions were most sensitive to occlusion of the IVth arches. To evaluate these simulations experimentally, a novel in vivo experimental model of pharyngeal arch occlusion was developed and implemented using two-photon microscopy-guided femtosecond laser-based photodisruption surgery. The right IVth arch was occluded at HH18, and resulting diameter changes were followed for up to 24 h. Pharyngeal arch diameter responses to acute hemodynamic changes were predicted qualitatively but poorly quantitatively. Chronic growth and adaptation to hemodynamic changes, however, were predicted in a subset of arches. Our findings suggest that this complex biodynamic process is governed through more complex forms of mechanobiological vascular growth rules. Other factors in addition to wall shear stress or more complex WSS rules are likely important in the long-term arterial growth and patterning. Combination in silico/experimental platforms are essential for accelerating our understanding and prediction of consequences from embryonic/fetal cardiovascular occlusions and lay the foundation for noninvasive methods to guide CHD diagnosis and fetal intervention.
Asunto(s)
Aorta Torácica/embriología , Aorta Torácica/fisiopatología , Enfermedades Vasculares/embriología , Enfermedades Vasculares/fisiopatología , Animales , Región Branquial/fisiología , Embrión de Pollo , Pollos , Simulación por Computador , Hemodinámica/fisiología , Modelos Cardiovasculares , Fotones , Resistencia al CorteRESUMEN
Vascular anomalies can be detected in utero and should be considered in the setting of solid, mixed or cystic lesions in the fetus. Evaluation of the gray-scale and color Doppler US and MRI characteristics can guide diagnosis. We present a case-based pictorial essay to illustrate the prenatal imaging characteristics in 11 pregnancies with vascular malformations (5 lymphatic malformations, 2 Klippel-Trenaunay syndrome, 1 venous-lymphatic malformation, 1 Parkes-Weber syndrome) and vascular tumors (1 congenital hemangioma, 1 kaposiform hemangioendothelioma). Concordance between prenatal and postnatal diagnoses is analyzed, with further discussion regarding potential pitfalls in identification.
Asunto(s)
Diagnóstico Prenatal , Enfermedades Vasculares/diagnóstico , Malformaciones Vasculares/diagnóstico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Embarazo , Ultrasonografía Doppler , Ultrasonografía Prenatal , Enfermedades Vasculares/embriología , Malformaciones Vasculares/embriologíaRESUMEN
BACKGROUND: Phase-contrast MRI with metric-optimized gating is a promising new technique for studying the distribution of the fetal circulation. However, mean and reference ranges for blood flow measurements made in the major fetal vessels using this technique are yet to be established. METHODS AND RESULTS: We measured flow in the major vessels of the fetal circulation in 40 late-gestation normal human fetuses using phase-contrast MRI (mean gestational age, 37 [SD=1.1] weeks). Flows were indexed to the fetal weight, which was estimated from the fetal volume calculated by MRI segmentation. The following mean flows (in mL/min per kilogram; ±2SD) were obtained: combined ventricular output, 465 (351, 579); main pulmonary artery, 261 (169, 353); ascending aorta, 191 (121, 261); superior vena cava, 137 (77, 197); ductus arteriosus, 187 (109, 265); descending aorta, 252 (160, 344); pulmonary blood flow, 77 (0, 160); umbilical vein, 134 (62, 206); and foramen ovale, 135 (37, 233). Expressed as percentages of the combined ventricular output, the mean flows±2 SD were as follows: main pulmonary artery, 56 (44, 68); ascending aorta, 41 (29, 53); superior vena cava, 29 (15, 43); ductus arteriosus, 41 (25, 57); descending aorta, 55 (35, 75); pulmonary blood flow, 16 (0, 34); umbilical vein, 29 (11, 47); and foramen ovale, 29 (7, 51). A strong inverse relationship between foramen ovale shunt and pulmonary blood flow was noted (r=-0.64; P<0.0001). CONCLUSIONS: Although too small a sample size to provide normal ranges, these results are in keeping with those predicted in humans based on measurements made in fetal lambs using radioactive microspheres and provide preliminary reference ranges for the late-gestation human fetuses. The wide range we found in foramen ovale shunting suggests a degree of variability in the way blood is streamed through the fetal circulation.
Asunto(s)
Arterias/fisiología , Feto/irrigación sanguínea , Imagen por Resonancia Cinemagnética/métodos , Diagnóstico Prenatal/métodos , Flujo Sanguíneo Regional/fisiología , Enfermedades Vasculares/diagnóstico , Adulto , Arterias/embriología , Estudios Transversales , Femenino , Enfermedades Fetales/diagnóstico , Enfermedades Fetales/fisiopatología , Edad Gestacional , Humanos , Embarazo , Estudios Prospectivos , Valores de Referencia , Reproducibilidad de los Resultados , Enfermedades Vasculares/embriología , Enfermedades Vasculares/fisiopatologíaRESUMEN
OBJECTIVE: To assess the value of gestational age and cardiovascular Doppler indices in predicting perinatal mortality in a multicenter cohort of early-onset intrauterine growth-restricted (IUGR) fetuses. METHODS: A multicenter prospective cohort study including 157 early-onset (<34 weeks) IUGR cases with abnormal umbilical artery (UA) Doppler was conducted. Cardiovascular assessment included the ductus venosus (DV), the aortic isthmus flow index (IFI), and the myocardial performance index (MPI). Isolated and combined values to predict the risk of perinatal death were evaluated by logistic regression and by decision tree analysis, where the gestational age at delivery, UA, and middle cerebral artery (MCA) were also included as covariates. RESULTS: Perinatal mortality was 17% (27/157). All parameters were significantly associated with perinatal death, with individual odds ratios (OR) of 25.2 for gestational age below 28 weeks, 12.1 for absent/reversed DV atrial flow, 5.3 for MCA pulsatility index <5th centile, 4.6 for UA absent/reversed diastolic end-flow, 1.8 for IFI <5th centile, and 1.6 for MPI >95th centile. Decision tree analysis identified gestational age at birth as the best predictor of death (<26 weeks, 93% mortality; 26-28 weeks, 29% mortality, and >28 weeks, 3% mortality). Between 26 and 28 weeks, DV atrial flow allowed further stratification between high (60%) and low risk (18%) of mortality. CONCLUSIONS: Gestational age largely determines the risk of perinatal mortality in early-onset IUGR before 26 weeks and later than 28 weeks of gestation. The DV may improve clinical management by stratifying the probability of death between 26 and 28 weeks of gestation.
Asunto(s)
Retardo del Crecimiento Fetal/mortalidad , Retardo del Crecimiento Fetal/fisiopatología , Edad Gestacional , Arterias Umbilicales/anomalías , Arterias Umbilicales/diagnóstico por imagen , Enfermedades Vasculares/diagnóstico por imagen , Enfermedades Vasculares/etiología , Aorta/anomalías , Aorta/diagnóstico por imagen , Aorta/embriología , Aorta/fisiopatología , Bélgica/epidemiología , Chile/epidemiología , Estudios de Cohortes , Femenino , Desarrollo Fetal , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Arteria Cerebral Media/anomalías , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/embriología , Arteria Cerebral Media/fisiopatología , Embarazo , Estudios Prospectivos , Riesgo , España/epidemiología , Ultrasonografía Doppler , Ultrasonografía Prenatal , Arterias Umbilicales/embriología , Arterias Umbilicales/fisiopatología , Enfermedades Vasculares/embriología , Enfermedades Vasculares/fisiopatologíaRESUMEN
OBJECTIVE: We aimed to illustrate the histogenesis, lactic dehydrogenase isoenzymes electrophoresis, and DNA damage of cardiac muscles and blood vessels during prenatal life of maternal diabetic or hypercholesterolemic mother. METHODS: Eighty fertile male and virgin female Wistar rats (1 male/3 females), weighing approximately 130 g, were mated and zero date of gestation was determined. Diabetes was induced at the fifth day of gestation by intraperitoneal injection of a single dose of 60 mg streptozotocin/kg body weight in citrate buffer, pH 4.6. At the same time, hypercholesterolemia was carried out by feeding virgin rats a diet containing 3% cholesterol for 6 wk before the onset of conception. Pregnant rats were arranged into three groups: control, diabetic, and hypercholesterolemic (n = 20). The animals were sacrificed and embryos were separated at 7-, 13-, 15-, 17-, and 19 d old, respectively, and subjected to light and transmission electron microscopy, lactic dehydrogenases isoenzymes electrophoresis, DNA fragmentation, and comet assay. The sera of the mothers were examined for fasting glucose level, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, and creatine phosphokinase levels. RESULTS: Diabetic and hypercholesterolemic mothers exhibited a significant increase of sera cholesterol level, low-density lipoprotein, and creatine phosphokinase activity. Histologic findings of embryos of diabetic and hypercholesterolemic mothers revealed cardiomyopathy and malformation of blood vessels with an apparent degeneration of their endothelium. Transmission electron microscopy possessed massive necrosis of muscle fibers, disorganization of Z and I bands, and mitochondrial damage. Lactic dehydrogenase isoenzyme electrophoresis was altered and genomic DNA fragmentation was markedly increased. CONCLUSION: Maternal diabetes or hypercholesterolemia led to marked alterations in blood vessel differentiation as well as to cardiomyopathy during prenatal growth as assessed by the disruption of fine structures, abnormal lactic dehydrogenase isoenzymes electrophoresis, and an increase of DNA damage. These may be attributed to the marked oxidative stress and liberation of free oxygen radicals, which interrupted the myocardium structure and function during organogenesis.
Asunto(s)
Cardiomiopatías/etiología , Diabetes Mellitus Experimental/fisiopatología , Desarrollo Embrionario , Hipercolesterolemia/fisiopatología , Neovascularización Fisiológica , Complicaciones del Embarazo/fisiopatología , Enfermedades Vasculares/etiología , Animales , Vasos Sanguíneos/embriología , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/ultraestructura , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/embriología , Cardiomiopatías/metabolismo , Daño del ADN , Diabetes Mellitus Experimental/sangre , Endotelio Vascular/embriología , Endotelio Vascular/ultraestructura , Femenino , Hipercolesterolemia/sangre , Isoenzimas/metabolismo , Lactato Deshidrogenasas/metabolismo , Mitocondrias Musculares/ultraestructura , Fibras Musculares Esqueléticas/ultraestructura , Miometrio/embriología , Miometrio/metabolismo , Miometrio/ultraestructura , Embarazo , Complicaciones del Embarazo/sangre , Ratas , Ratas Wistar , Ultrasonografía , Enfermedades Vasculares/diagnóstico por imagen , Enfermedades Vasculares/embriología , Enfermedades Vasculares/metabolismoRESUMEN
The purpose of this pictorial review is to understand the embryological basis of the development of congenital hepatic vascular shunts and to review the multimodality imaging appearances of congenital and acquired hepatic vascular shunts. Hepatic vascular shunts are commonly seen in imaging. Familiarity with their characteristic appearances is important in order to accurately characterise these shunts and diagnose the underlying disorders.
Asunto(s)
Angiografía , Venas Hepáticas/diagnóstico por imagen , Hígado/diagnóstico por imagen , Vena Porta/diagnóstico por imagen , Enfermedades Vasculares/diagnóstico por imagen , Venas Hepáticas/anomalías , Venas Hepáticas/fisiopatología , Humanos , Hígado/irrigación sanguínea , Hígado/embriología , Vena Porta/anomalías , Vena Porta/fisiopatología , Enfermedades Vasculares/embriología , Enfermedades Vasculares/fisiopatologíaRESUMEN
Cerebral cavernous malformations (CCMs) are a prevalent class of vascular anomalies characterized by thin-walled clusters of malformed blood vessels in the brain. Heritable forms are caused by mutations in CCM1, CCM2 and CCM3, but despite the importance of these factors in vascular biology, an understanding of their molecular and cellular functions remains elusive. Here we describe the characterization of a zebrafish embryonic model of CCM. Loss of ccm1 in zebrafish embryos leads to severe and progressive dilation of major vessels, despite normal endothelial cell fate and number. Vascular dilation in ccm1 mutants is accompanied by progressive spreading of endothelial cells and thinning of vessel walls despite ultrastructurally normal cell-cell contacts. Zebrafish ccm2 mutants display comparable vascular defects. Finally, we show that ccm1 function is cell autonomous, suggesting that it is endothelial cellular morphogenesis that is regulated by CCM proteins during development and pathogenesis.
Asunto(s)
Vasos Sanguíneos/crecimiento & desarrollo , Endotelio/crecimiento & desarrollo , Proteínas Asociadas a Microtúbulos/metabolismo , Morfogénesis , Enfermedades Vasculares/metabolismo , Proteínas de Pez Cebra/metabolismo , Pez Cebra/metabolismo , Animales , Vasos Sanguíneos/embriología , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiopatología , Endotelio/embriología , Endotelio/metabolismo , Endotelio/fisiopatología , Regulación del Desarrollo de la Expresión Génica , Humanos , Proteínas Asociadas a Microtúbulos/genética , Modelos Animales , Proteínas Musculares , Mutación , Fenotipo , Enfermedades Vasculares/embriología , Enfermedades Vasculares/genética , Pez Cebra/embriología , Pez Cebra/genética , Pez Cebra/crecimiento & desarrollo , Proteínas de Pez Cebra/genéticaRESUMEN
Cardiovascular-related diseases are the leading cause of death in the world in both men and women. In addition to the environmental and genetic factors, early life conditions are now also considered important contributing elements to these pathologies. The concept of 'fetal' or 'developmental' origins of adult diseases has received increased recognition over the last decade, yet the mechanism by which altered perinatal environment can lead to dysfunction mostly apparent in the adult are incompletely understood. This review will focus on the mechanisms and pathways that epidemiological studies and experimental models have revealed underlying the adult cardiovascular phenotype dictated by the perinatal experience, as well as the probable key causal or triggering elements. Programmed elevated blood pressure in the adult human or animal is characterized by vascular dysfunction and microvascular rarefaction. Developmental mechanisms that have been more extensively studied include glucocorticoid exposure, the role of the kidneys and the renin-angiotensin system. Other pathophysiological pathways have been explored, such as the role of the brain and the sympathetic nervous system, oxidative stress and epigenetic changes. As with many complex diseases, a unifying hypothesis linking the perinatal environment to elevated blood pressure and vascular dysfunction in later life cannot be presumed, and a better understanding of those mechanisms is critical before clinical trials of preventive or 'deprogramming' measures can be designed.
Asunto(s)
Enfermedades Cardiovasculares/etiología , Efectos Tardíos de la Exposición Prenatal , Adulto , Animales , Enfermedades Cardiovasculares/embriología , Modelos Animales de Enfermedad , Femenino , Desarrollo Fetal , Humanos , Hipertensión/embriología , Hipertensión/etiología , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Estrés Oxidativo , Embarazo , Enfermedades Vasculares/embriología , Enfermedades Vasculares/etiologíaRESUMEN
Developmental programming of hypertension is associated with vascular dysfunction characterized by impaired vasodilatation to nitric oxide, exaggerated vasoconstriction to ANG II, and microvascular rarefaction appearing in the neonatal period. Hypertensive adults have indices of increased oxidative stress, and newborns that were nutrient depleted during fetal life have decreased antioxidant defenses and increased susceptibility to oxidant injury. To test the hypothesis that oxidative stress participates in early life programming of hypertension, vascular dysfunction, and microvascular rarefaction associated with maternal protein deprivation, pregnant rats were fed a normal, low protein (LP), or LP plus lazaroid (lipid peroxidation inhibitor) isocaloric diet from the day of conception until delivery. Lazaroid administered along with the LP diet prevented blood pressure elevation, enhanced vasomotor response to ANG II, impaired vasodilatation to sodium nitroprusside, and microvascular rarefaction in adult offspring. Liver total glutathione was significantly decreased in LP fetuses, and kidney eight-isoprostaglandin F2alpha (8-isoPGF(2alpha)) levels were significantly increased in adult LP offspring; these modifications were prevented by lazaroid. Renal nitrotyrosine abundance and blood levels of 1,4-dihydroxynonene and 4-hydroxynonenal-protein adducts were not modified by antenatal diet exposure. This study shows in adult offspring of LP-fed dams prevention of hypertension, vascular dysfunction, microvascular rarefaction, and of an increase in indices of oxidative stress by the administration of lazaroid during gestation. Lazaroid also prevented the decrease in antioxidant glutathione levels in fetuses, suggesting an antenatal mild oxidative stress in offspring of LP-fed dams. These studies support the concept that perinatal oxidative insult can lead to permanent alterations in the cardiovascular system development.
Asunto(s)
Envejecimiento/fisiología , Antioxidantes/farmacología , Vasos Sanguíneos/efectos de los fármacos , Dieta con Restricción de Proteínas/efectos adversos , Hipertensión , Efectos Tardíos de la Exposición Prenatal , Enfermedades Vasculares , Animales , Animales Recién Nacidos , Antioxidantes/administración & dosificación , Vasos Sanguíneos/fisiopatología , Femenino , Hipertensión/etiología , Hipertensión/patología , Hipertensión/fisiopatología , Hipertensión/prevención & control , Estrés Oxidativo/efectos de los fármacos , Embarazo , Ratas , Enfermedades Vasculares/embriología , Enfermedades Vasculares/etiología , Enfermedades Vasculares/patología , Enfermedades Vasculares/fisiopatologíaRESUMEN
Absence of the right superior vena cava (SVC) is a rare event occurring in patients without congenital cardiovascular abnormalities. Since absence of the right SVC is usually clinically silent, its diagnosis is mandatory prior to invasive medical or surgical procedures. We report two cases of echocardiographic diagnosis of absence of the right SVC with persistent left SVC and a large coronary sinus in structurally normal heart in a fetus of 20 weeks' gestation and in a newborn. The diagnosis was confirmed by transthoracic contrast echocardiography with intravenous injection of agitated saline into the right arm.
Asunto(s)
Ecocardiografía , Ultrasonografía Prenatal/métodos , Enfermedades Vasculares/diagnóstico por imagen , Vena Cava Superior/anomalías , Diagnóstico Diferencial , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Enfermedades Vasculares/congénito , Enfermedades Vasculares/embriología , Vena Cava Superior/diagnóstico por imagen , Vena Cava Superior/embriologíaRESUMEN
In hypertension, increased peripheral vascular resistance results from vascular dysfunction with or without structural changes (vessel wall remodeling and/or microvascular rarefaction). Humans with lower birth weight exhibit evidence of vascular dysfunction. The current studies were undertaken to investigate whether in utero programming of hypertension is associated with in vivo altered response and/or abnormal vascular structure. Offspring of Wistar dams fed a normal (CTRL) or low (LP)-protein diet during gestation were studied. Mean arterial blood pressure response to ANG II was significantly increased, and depressor response to sodium nitroprusside (SNP) infusions significantly decreased in male LP adult offspring relative to CTRL. No arterial remodeling was observed in male LP compared with CTRL offspring. Capillary and arteriolar density was significantly decreased in striated muscles from LP offspring at 7 and 28 days of life but was not different in late fetal life [day 21 of gestation (E21)]. Angiogenic potential of aortic rings from LP newborn (day of birth, P0) was significantly decreased. Striated muscle expressions (Western blots) of ANG II AT(1) receptor subtype, endothelial nitric oxide synthase, angiopoietin 1 and 2, Tie 2 receptor, vascular endothelial growth factor and receptor, and platelet-derived growth factor C at E21 and P7 were unaltered by antenatal diet exposure. In conclusion, blood pressure responses to ANG II and SNP are altered, and microvascular structural changes prevail in this model of fetal programming of hypertension. The capillary rarefaction is absent in the fetus and appears in the neonatal period, in association with decreased angiogenic potential. The study suggests that intrauterine protein restriction increases susceptibility to postnatal factors resulting in microvascular rarefaction, which could represent a primary event in the genesis of hypertension.
Asunto(s)
Dieta con Restricción de Proteínas/efectos adversos , Hipertensión/patología , Hipertensión/fisiopatología , Microcirculación/patología , Microcirculación/fisiopatología , Neovascularización Patológica/patología , Neovascularización Patológica/fisiopatología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Animales , Susceptibilidad a Enfermedades/embriología , Susceptibilidad a Enfermedades/patología , Susceptibilidad a Enfermedades/fisiopatología , Femenino , Hipertensión/embriología , Hipertensión/etiología , Masculino , Neovascularización Patológica/embriología , Embarazo , Efectos Tardíos de la Exposición Prenatal/patología , Ratas , Ratas Wistar , Enfermedades Vasculares/embriología , Enfermedades Vasculares/etiología , Enfermedades Vasculares/patología , Enfermedades Vasculares/fisiopatologíaRESUMEN
Determining how the pulmonary vascular system is formed, maintained, or disrupted during development and disease represents a major challenge in contemporary lung biology. Whereas it is appreciated that cellular proliferation, differentiation, migration, and apoptosis need to be carefully controlled in order to attain pulmonary vascular homeostasis, knowledge of the underlying cellular and molecular mechanisms involved remains surprisingly limited. Because homeobox genes represent master regulators of organogenesis and tissue patterning, it is likely that these transcription factors play a critical role in the formation of blood vessels within the lung, as well as in pathologic states in which the highly ordered structure of the pulmonary vascular tree is compromised. The aim of this review is to discuss some of the known functions of homeobox genes in the vasculature, and to extrapolate these findings to their potential roles in developing and diseased pulmonary vessels.
Asunto(s)
Genes Homeobox/fisiología , Pulmón/irrigación sanguínea , Circulación Pulmonar/fisiología , Enfermedades Vasculares/fisiopatología , Animales , Homeostasis , Humanos , Pulmón/embriología , Pulmón/crecimiento & desarrollo , Circulación Pulmonar/genética , Ovinos , Enfermedades Vasculares/embriología , Enfermedades Vasculares/genéticaRESUMEN
Glucose intolerance in adults born with intrauterine growth retardation (IUGR) may involve peripheral insulin resistance and/or abnormal endocrine pancreas development during fetal life. We quantified insulin-containing cells in deceased human fetuses with IUGR (<10th percentile, n = 21) or normal growth (control fetuses, n = 15). Paraffin-embedded pancreatic tissues from fetuses older than 32 weeks were obtained from two fetopathology departments. Mean gestational age was 36 weeks in both groups. Tissues with lysis and those fetuses with defects, aneuploidy, or genetic abnormalities were excluded. For each subject, six pancreatic sections spaced evenly throughout the organ were immunostained with anti-insulin antibody. Total tissue and insulin-positive areas were measured by computer-assisted quantitative morphometry. Results were expressed in percentages. To evaluate islet morphogenesis, the percentages of beta-cells inside and outside islets were determined. Islet density was similar in the two groups (P = 0.86). The percentage of pancreatic area occupied by beta-cells (beta-cell fraction) was not correlated with gestational age (r = 0.06 and P = 0.97 in IUGR fetuses; r = 0.12 and P = 0.67 in control fetuses) or body weight (r = 0.16 and P = 0.47 in IUGR fetuses; r = 0.24 and P = 0.39 in control fetuses). Mean beta-cell fraction was 2.53% in the IUGR fetuses and 2.86% in the control fetuses (P = 0.47). The percentage of beta-cells located within islets was identical in the two groups (mean 35%). Our data militate against a primary developmental pancreatic abnormality in human IUGR, leaving peripheral insulin resistance as the most likely mechanism of glucose intolerance in adults born with IUGR.
Asunto(s)
Retardo del Crecimiento Fetal/embriología , Islotes Pancreáticos/embriología , Estudios de Cohortes , Desarrollo Embrionario y Fetal , Retardo del Crecimiento Fetal/complicaciones , Peso Fetal , Feto/anatomía & histología , Feto/metabolismo , Edad Gestacional , Humanos , Insulina/metabolismo , Tamaño de los Órganos , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/embriologíaRESUMEN
Major congenital malformations, including those affecting the cardiovascular system, remain the leading cause of mortality and morbidity in infants of diabetic mothers. Interestingly, targeted mutations of several genes (including VEGF and VEGF receptors) and many teratogenic agents (including excess D-glucose) that give rise to embryonic lethal phenotypes during organogenesis are associated with a failure in the formation and/or maintenance of a functional vitelline circulation. Given the similarities in the pathology of the abnormal vitelline circulation in many of these conditions, we hypothesized that the hyperglycemic insult present in diabetes could cause the resultant abnormalities in the vitelline circulation by affecting VEGF/VEGF receptor signaling pathway(s). In this study we report that hyperglycemic insult results in reduced levels of VEGF-A in the conceptus, which in turn, leads to abnormal VEGF receptor signaling, ultimately resulting in embryonic (vitelline) vasculopathy. These findings and our observation that addition of exogenous rVEGF-A(165) within a defined concentration range blunts the hyperglycemia-induced vasculopathy in the conceptus support the concept that VEGF levels can be modulated by glucose levels. In addition, these findings may ultimately lead to novel therapeutic approaches for the treatment of selected congenital cardiovascular abnormalities associated with diabetes.