Appropriate arterial function and structure are vital for a proper cardiovascular performance and therefore fundamental for a healthy life. Arterial function depends on cellular and molecular mechanisms but as well on the structural features. In fact, it has been shown that structural and biomechanical properties of vessels are very much related to several cardiovascular pathologies, such as systemic and pulmonary hypertension. Chronic lack of oxygen (hypoxia), may determine an impairment of the cardiovascular function, potentially deriving in pulmonary/systemic hypertension and cardiac failure. This is particularly relevant in human populations exposed to high altitude (above 2500m), either in chronic continuous (permanent inhabitants) or chronic intermittent (shifts of high altitude workers, such as miners, custom agents astronomers; and mountaineers) fashions. Most of the studies about vascular effects of chronic hypoxia have focused on function and molecular mechanisms involved in the pathophysiological responses. However, few is known about the biomechanical responses of systemic, pulmonary and cerebral arteries in these conditions, particularly in the chronic exposure to hypoxia as it happens in high-altitude population and in several diseases in lowlanders. The main goal of this project is to determine the vascular biomechanical characteristics of a representative rat paradigm of living under hypoxia and, in addition, establish the modelling, numerical simulation and experimental validation of the biomechanical responses of arterial vessels.
Specifically, three different types of vessels (aorta, carotid and femoral), at different age (neonates, juveniles and adults)
will be analyzed, either under normoxic, chronic permanent hypoxic or chronic intermittent hypoxic conditions.
Small rodents have been extensively used as a paradigm of cardiovascular and vascular function, allowing massive
steps in the knowledge of mechanisms involved in cardiovascular pathologies. Using a rat model, we will deeply analyze
the biomechanical properties of the vasculature of animals exposed to chronic hypoxia (permanent or intermittent) in a
hypobaric chamber, adding substantial data for the comprehension of the vascular biomechanical behaviour under these
conditions.
The need for a better understanding of the biomechanical response of arteries leads to the development of constitutive
models that may define realistic and reliable stress-strain relationships. In this project, several constitutive models aimed
at describing the biomechanical behaviour of soft tissues will be assessed. The specific aspects to be taken into account
of the vessels biomechanical characterisation are: incompressibility of the tissue, presence of large deformations, isotropic and anisotropic material behaviours, residual stresses, rate dependent (i.e., viscous) effects, damage and active response. The material characterisation of the biomechanical behaviour of rat arteries will be performed via in-vitro biaxial and myograph tensile tests and ring opening test, considering standard, cyclic and relaxation loading conditions. From these experiments, the material characterisation will also involve the derivation of the material parameters. Specifically, we will address the development of algorithms for the treatment of non-linearities in the fitting procedure and sensitivity analysis to determine the consistency of the parameters found with this methodology. The analysis will also include comparison between the numerical predictions of the different constitutive models in their application to experimental data to be measured in this project.
The analysis of the response of pressurised straight arterial vessels will be additionally carried out. Importantly, this
test mimics the in-vivo physiological conditions of the arterial vessel. Aside from the internal pressure, axial stretching is
usually considered. As a non-uniform biaxial stress state is commonly developed in this test, this fact extends the validity of the material characterisation. The material response will be described via the constitutive models previously characterised. Due to the complex stress and strain patterns developed in this problem, numerical simulations defined in the context of the finite element method will be performed. The obtained numerical results will be validated with the corresponding experimental measurements. Moreover, we expect to characterise the biomechanical properties of different vascular beds, representatives of systemic, pulmonary and cerebral circulations. We shall also describe the effects of chronic hypoxia on these properties. Furthermore, we will perform histological analyses to assess the ultrastructure and the wall components of the intima, media and adventitia layers and relate them with the biomechanical findings.
The outcomes of this project will enhance the knowledge necessary to integrate the functional, structural and
biomechanical properties of vascular tissues. Clearly, our data will provide useful information not only for vascular pathophysiology understanding, but also for optimization of medical diagnosis, prognosis and potential therapeutic approaches to the related pathologies

As a scientist in Chile, I have been focused on understanding the mechanisms underlying fetal vascular dysfunction associated with altered fetal growth with a special interest in impaired fetal growth and epigenetic regulation. Fetal growth restriction (FGR), commonly defined by a weight below the 10th percentile is associated with increased perinatal morbidity and mortality with an incidence of 3 to 10% of all live births1, 2. Therefore, FGR remains at the forefront of basic science and clinical investigation, as it poses a significant problem on every nation’s wealth and health. Adverse conditions in complicated pregnancy known to induce FGR include reductions in fetal oxygenation or chronic fetal hypoxia3. Several studies in humans have established that high altitude pregnancy reduces fetal growth 4-6. Further, several studies in mammalian animal models of hypoxic pregnancy have also reported a significant effect in slowing fetal growth7. However, since most high altitude populations are also impoverished with a high prevalence of maternal undernutrition and since hypoxic exposure of mammalian animals during pregnancy can reduce maternal food intake7, the partial contributions of fetal under-nutrition versus fetal under-oxygenation in promoting FGR remain uncertain.
The Giussani group at the University of Cambridge have combined the chick embryo model with hypoxic incubation to isolate the direct effects of chronic fetal hypoxia in promoting FGR. This group has shown that incubation at high altitude of fertilized eggs laid by sea level hens leads to FGR. Conversely, incubation at sea level of fertilized eggs laid by high altitude hens that normally show FGR completely recovered fetal growth. Importantly, incubation at high altitude of fertilized eggs laid by sea level with oxygen supplementation also prevented FGR8. Recent studies by the Cambridge group have also reported that isobaric rather than hypobaric chronic fetal hypoxia also leads to FGR in the chick embryo9. Further, they have reported that FGR as a result of isolated chronic fetal hypoxia is associated with significant oxidative stress and endothelial dysfunction in fetal peripheral circulations. Treatment of chick embryos during hypoxic incubation with the antioxidant melatonin rescued the endothelial dysfunction in peripheral circulations by the end of the incubation period. The mechanisms involved included reduced oxidative stress, enhanced antioxidant capacity, restored vascular endothelial growth factor expression and increased NO bioavailability9. Combined, therefore, studies by the Cambridge group have isolated a direct effect of hypoxia in promoting FGR and fetal endothelial dysfunction independent of effects at the level of the placenta or the mother and suggest that antioxidant therapy may also have a direct protective effect on the fetus.
These findings are of particular interest to me because my research group in Chile has recently established a guinea pig experimental model of FGR. This is by progressive bilateral occlusion of the uterine arteries during the second half of gestation that gradually increases placental vascular resistance10, 11. Using this guinea pig model, we have recently shown that FGR induces epigenetic programming of eNOS expression in the fetal endothelium, which is prevented by a maternal treatment with N-acetylcysteine11. However, whether the effects of increased placental vascular resistance on the fetal epigenetic programming of eNOS expression is due to fetal under-nutrition versus fetal under-oxygenation in this model of FGR again remains uncertain. Therefore, the aim of my research proposal is to use the Cambridge chick embryo model of FGR as a result of hypoxic incubation to isolate the direct effects of chronic fetal hypoxia on epigenetic regulation promoting fetal vascular dysfunction. This would be the first step to enable better identification of potential targets for clinical intervention designed to protect the developing fetal circulation in pregnancy complicated by FGR and chronic fetal hypoxia.

Adverse intrauterine conditions, such as fetal growth restriction (FGR), increase the risk to develop cardiometabolic diseases in the adulthood. This concept has been called ‘Developmental Origins of Health and Disease’ (DOHaD) and relies on the activation of mechanisms sensing and signaling a diversity of stimuli during early development that later leads to higher risk of disease. The mechanisms that have been broadly suggested to be involved in these processes are epigenetic modifications in key gene promoters that could ‘record’ normal and abnormal perinatal stimuli. Intrauterine oxidative stress and chronic hypoxia are common features in FGR. Several cellular processes require the participation of pro-oxidant molecules which are normally neutralized by antioxidant defenses. However, under determined conditions, such as chronic hypoxia, the pro-oxidants overcome these defenses inducing oxidative stress. The latter is an important stimulus that regulates vascular function and cardiovascular physiology, playing a key role in the development of cardiovascular diseases, regulating negatively the bioavailability of the main vasodilator nitric oxide (NO). In addition, the vascular system presents a high phenotypic plasticity during life, which is modulated and restricted by epigenetic mechanisms (including DNA methylation, histone post-translational modifications, and micro RNAs).
The higher cardiovascular risk in adults born with FGR can be traced back to a reduced arterial compliance in pre-pubertal subjects and a decreased peripheral endothelial-dependent vascular relaxation at birth. This endothelial dysfunction (ED) is also observed in FGR placental vessels, suggesting an early onset of ED that could be evidenced in systemic and placental arteries. Our studies in human placentae have demonstrated that ED in FGR can be modulated by oxidative stress and is associated with changes in proteome profile as well as an epigenetic-mediated regulation of eNOS expression. Similarly, in guinea pigs, we have found that ED in FGR is also occurring in the fetal arteries and is prevented by maternal treatment with antioxidants. Analysis of eNOS expression and Nos3 promoter DNA methylation profile in endothelial cells from the aorta and umbilical arteries of FGR guinea pigs shows common molecular markers of ED in FGR systemic and umbilical vessels which are reverted by a maternal antioxidant treatment. Altogether, these data support the role of oxidative stress in the epigenetic programming of ED in FGR and the potential predictive value of studying human umbilical arteries endothelial cells (HUAEC). However, there are no studies addressing the time course and origins of the ED in FGR and the participation of additional epigenetic mechanisms, such as miRNAs, in this process.
Here, we put forward two inter-related hypotheses. First, that arterial endothelium from babies with FGR show a genomic DNA methylation signature along with an altered expression of miRNAs miR-21, miR-126 & miR-155, which contributes to changes in the expression of enzymes related to NO synthesis, endothelial dysfunction, and vascular remodeling. Second, that FGR has, during gestation, dynamic changes in the expression of miRNAs miR-21, miR-126 & miR-155 as an early response to hypoxia and oxidative stress in the fetus leading, in the long term, to endothelial dysfunction and vascular remodeling. These hypothesis will be tested in primary cultures of HUAEC from FGR neonates and validated using guinea pig and chick embryo models of FGR according to the following general aims (GA): GA-1 To demonstrate, in human umbilical artery endothelial cells, whether FGR is associated with an altered epigenetic regulation (i.e. increased levels of miR-21, miR-126 & miR-155 and a differential genomic DNA methylation) of NO-related enzymes (i.e. eNOS, DDAH1, Nrf2, Arg2, and HO-1), which modifies the response to hypoxia and impairs angiogenic capacity.GA-2 To demonstrate, in FGR guinea pigs, whether circulating levels of miR-21, miR-126 & miR-155 are dynamically regulated during the development of fetal vascular dysfunction and if the prevention of oxidative stress by an antioxidant administration to mothers, contributes to this regulation. GA-3 To demonstrate, in FGR chicken embryos, whether the silencing of miR-21, miR-126 and miR-155 expression modifies the endothelial and vascular dysfunction induced by chronic hypoxia and oxidative stress. Our expected outcome is to demonstrate that miRNAs miR-21, miR-126 & miR-155 participates in the early defense to hypoxia and oxidative stress in the FGR, but leading at long-term to ED. Further, we propose that regulation of these miRNAs during gestation could prevent these effects. This project is not only relevant to uncover the developmental mechanisms that determine short- and long-term vascular dysfunction, but also to open potential approaches for treatments in complicated pregnancies in humans. Combined, our program of work offers insights into mechanisms underlying the association between intrauterine hypoxia, oxidative stress and the increased risk of developing cardiovascular disease in later life, and possible interventions considering administration of therapeutic agents at critical stages of intrauterine development.

En la actualidad existe evidencia convincente del limitado impacto que tienen las estrategias destinadas a la prevención y tratamiento de la hipertensión y otras enfermedades cardiovasculares, una vez que éstas se manifiestan en el adulto. En este sentido, la identificación de los mecanismos que determinan a lo largo de la vida, especialmente en etapas tempranas del desarrollo, una mayor susceptibilidad a la aparición de estas enfermedades, representan un desafío para implementar estrategias efectivas de prevención o, alternativas terapéuticas adecuadas al grado de compromiso de la salud. Considerando la gran influencia que muestra la trayectoria de crecimiento y el estilo de vida sobre el desarrollo de enfermedades vasculares e hipertensión, en los últimos años ha existido un creciente interés en definir la participación de mecanismos que modifican la expresión de genes sin alterar la secuencia de estos (i.e. mecanismos epigenéticos) sobre el origen y progreso de éstas. El presente capítulo abordará qué es la epigenética, los mecanismos que median dichos efectos y el rol que cumple en definir a nivel molecular la programación de la(s) respuestas fisiológicas que condicionan el riesgo de desarrollar obesidad en las diferentes etapas del ciclo vital.
La visión de los factores genéticos como causa de las enfermedades crónicas, incluyendo las cardiovasculares, ha sido el motor de la investigación biomédica en el último siglo. Sin embargo, el padre de la biología moderna, Charles Darwin, planteó fuertemente en su obra “El origen de las Especies mediante la Selección Natural” que la “ley superior” del origen de las especies es la adaptación a “las condiciones de existencia” (i.e. medioambiente, estilo de vida), la que estaría por sobre la “selección natural” de características heredables (i.e. genes). Posteriormente, sería Conrad Waddington en sus estudios de embriología quien propone la importancia de la interacción entre los genes y el ambiente. Lo que se manifiesta en la capacidad que tiene el organismo de generar, a partir un conjunto de genes (genoma) único, los distintos tipos y funciones celulares que lo constituyen, mediante respuestas a estímulos que se suceden en un tiempo y lugar específico. Dicha propiedad del medioambiente de moldear el fenotipo fue definida por Waddington como “epigenética”.
Actualmente se denomina como epigenética al conjunto de “mecanismos modificadores del DNA que regulan la plasticidad fenotípica de una célula u organismo”. A través de estos mecanismos, nuestros genes pueden expresarse de manera adecuada en respuesta a cambios en el ambiente; pero a la vez definen respuestas fisiológicas a mediano y largo plazo basados en estas señales entregadas por el ambiente. En este contexto, el establecimiento de dichas respuestas limitaría, a través del ciclo vital, la plasticidad fenotípica del individuo. La presente línea de investigación se ha propuesto estudiar los cambios estructurales del sistema vascular y la activación de mecanismos epigenéticos desde etapas tempranas de la vida, que contribuirían al desarrollo de enfermedades cardiovasculares en el adulto. En este sentido plantemos que “el desarrollo de hipertensión y enfermedades cardiovasculares en el adulto resultaría de un programación estructural y epigenética a nivel vascular, mediada por niveles deficitarios de oxígeno (i.e. hipoxia) y el estrés oxidativo intrauterino”. Esta programación fetal establecería una fisiología vascular pro-hipertensiva que devendría posteriormente en una disfunción cardiovascular a medida que el individuo envejece.

Las enfermedades cardiovasculares (ECV), incluidas la hipertensión, el accidente cerebrovascular y la enfermedad de las arterias coronarias, son las principales patologías a nivel mundial con un impacto significativo en la morbilidad y la mortalidad. El riesgo de enfermedades cardiovasculares se explica parcialmente por factores genéticos, pero en mayor medida por estímulos que tienen lugar durante el desarrollo temprano y el envejecimiento. La función vascular durante la vida está determinada principalmente por tensiones mecánicas resultantes de la presión sanguínea y el flujo, así como por vías de señalización activadas por la disponibilidad de oxígeno. En este contexto, alteraciones en las fuerzas de estiramiento (i.e. tensiones residuales circunferenciales y longitudinales de las arterias), la tensión de corte anormal (shear stress i.e: la fricción del flujo sanguíneo en la superficie arterial luminal) y la hipoxia (i.e. la disminución relativa de las presiones de oxígeno) son factores críticos en el desarrollo de ECV.
Los miembros de este proyecto se han centrado en áreas particulares de estos procesos, sin embargo, se requieren esfuerzos adicionales interdisciplinarios para entender de manera integral los mecanismos mecánicos y moleculares involucrados en los orígenes de la disfunción cardiovascular. Recientemente se ha descrito a PIEZO1, un canal de cationes no selectivo, como uno de los principales activadores de la relajación dependiente de endotelio en respuesta a la tensión de corte. Sin embargo, la regulación de éste, por parte de los estímulos descritos anteriormente, no ha sido aún explorada. La presente propuesta busca caracterizar, a través de un estudio con enfoques en biomecánica, fisiología y biología molecular, los cambios en la función del mecano-sensor PIEZO1, en respuesta a estímulos físicos y biológicos en células endoteliales de arteria umbilical humana, con el fin de identificar potenciales blancos de modulación de la función vascular en condiciones que promueven las ECV.

There are more than 41 million deaths per year worldwide, 71% of them are due to non-communicable diseases (NCDs), with cardiovascular (CV) causes taking the first place. Adverse intrauterine conditions increase the risk of developing NCDs during the life course, a phenomenon known as Developmental Origins of Health and Disease (DOHaD).
The most frequent and clinically relevant adverse condition during fetal life is intrauterine hypoxia (IH), which is associated with a high perinatal morbi-mortality. The molecular mechanisms that could be involve in IH causes and consequences are an important aspect in most of the pregnancies at high altitudes (> 2500m), and in 3-4% of the pregnancies with utero-placental complications at lowlands.
Nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) are endogenous gasotransmitters with vasodilator properties that can regulate cardiovascular functions. These gasotransmitters may be affected by intrauterine chronic hypoxia- induced oxidative stress, eliciting vascular programming and deriving in cardiovascular dysfunction along life course.
Although these gasotransmitters have shown to determine endothelial, smooth muscle and cardiac function, the role of them in the fetal programming CV dysfunction due to developmental hypoxia and their relationship with oxidative stress is still unknown.

Our hypothesis is that the intrauterine development in chronic hypoxia programms the gasotransmitters pathways (NO, CO and H2S) in the heart and blood vessels through oxidative stress, which impacts in the short, medium and long term cardiovascular function. Therefore, an oral treatment with antenatal melatonin will prevent the hypoxic-induced cardiovascular impairment.

In this proposal, we aim to study, in a well-characterized guinea pig model, the origins and outcomes of cardiovascular dysfunction resulting from IH, by characterizing the functional, structural and molecular aspects of vasoactive mechanisms dependent on endogenous gasotransmitters, in the heart and blood vessels. Moreover, as fetal growth restriction and cardiovascular programming are related with hypoxia induced-oxidative stress, we will implement an antenatal treatment with melatonin, a proved antioxidant, to test the prevention of IH-induced cardiovascular risks in the short-, mediate- and long-term.

To address these aims, we will study the effects of intrauterine chronic hypoxia and oxidative stress on the NO, CO and H2S related pathways of the cardiovascular system in guinea pigs. We will describe the NO, CO and H2S related pathways, its epigenetic changes and their roles as important regulators of function, structure and biomechanical properties of heart and vessels, under hypoxia induced-oxidative stress.

The aforementioned will be done in animals gestated under IH, with or without antenatal melatonin treatment, and follow the cardiovascular function from fetus to adulthood. The methodology is an in vivo non-invasive evaluation of the function and structure of the cardiovascular system (ultrasound); an ex vivo function and biomechanical characterization of heart and arteries (Langendorff, wire myography, biomechanical tests); and in vitro determinations of genetic, protein and epigenetic expression in heart and several vascular beds; at different stages of life.
These approaches will permit us to correlate and integrate the short-, mediate- and long-term cardiovascular effects related to the gasotransmitters pathways, in the offspring gestated under chronic hypoxia. In addition, we will evaluate a supported treatment with melatonin, to prevent intrauterine growth restriction and cardiovascular impairment after IH exposure, to test the relationship of gasotransmitters pathways with intrauterine oxidative stress.

We expect to unravel the mechanisms underlying IH- induced cardiovascular reprogramming focusing on oxidative stress and gasotransmitters, in order to potentiate melatonin treatment as a possible therapy in hypoxia related complicated pregnancies, either at high altitude or lowlands. This grant will effectively provide a valuable resource for the scientific and clinical community to pursue the understanding of cardiovascular NCDs programmed by intrauterine hypoxia, a worldwide burden still without effective therapeutic approach. Furthermore, this will add knowledge to the foundations for the development of novel therapies for intrauterine hypoxia, and the prevention of CV risk in fetuses, neonates and adults.

Proyecto que busca establecer los efectos de un suplemento en base a miel sobre la salud y el bienestar, así como la respuesta al tratamiento en personas con úlcera gástricas.

El desarrollo de herramientas para el an ́alisis de funciones vitales a trav ́es de im ́agenes representa un campo de creciente inter ́es, especialmente para el estudio de marcadores tempranos de diversas patolog ́ıas, as ́ı como el desarrollo de aplicaciones diagn ́osticas a mediano plazo. En este contexto, el an ́alisis de la funci ́on vascular, a lo largo del ciclo vital, continua siendo un ́area con un alta demanda de nuevas tecnolog ́ıas, debido a su gran impacto a nivel de salud en la poblaci ́on. Esta propuesta busca generar una l ́ınea de investigaci ́on actualmente casi inexistente en Chile, las im ́agenes ultras ́onicas m ́edicas. En particular, nos gustar ́ıa introducir en Chile una t ́ecnica recientemente propuesta, denominada microscop ́ıa de localizaci ́on por ultrasonido (ULM), tambi ́en conocida como im ́agenes de su ́per- resoluci ́on. Esta t ́ecnica puede crear im ́agenes del sistema circulatoria con una resoluci ́on nunca antes vista, lo que permite visualizar vasos sangu ́ıneos de hasta 5μm. As ́ı, nuestra propuesta posee dos grandes objetivos. El primero es Optimizar y robusteces los procesos involucrados en el desarrollo de las im ́agenes de su ́per-resoluci ́on ultras ́onicas, esto a trav ́es de Optimizar los par ́ametros de adquisici ́on de datos y de procesamiento con el fin de robustecer la generaci ́on de este tipo de im ́agenes. Nuestro segundo objetivo es generar im ́agenes de su ́per- resoluci ́on de la red vascular interna de placenta humana ex-vivo y a buscar candidatos a marcadores a partir de estas im ́agenes.
La ecograf ́ıa convencional es ampliamente usada en Chile y el mundo. Es preferida entre otras modalidades de im ́agenes (MRI, PET, TC) debido a su portabilidad, bajo costo, naturaleza no invasiva y a que utiliza radiaci ́on no ionizante, especialmente en condiciones como el embarazo, o en pacientes con manejo farmacol ́ogico complejo, entre otras. Recientemente, se han desarrollado nuevas modalidades de im ́agenes ultras ́onicas, propiciadas por la mejora en la industria de los semiconductores, lo que ha permitido un incremento en la capacidad de computo de los esc ́aneres ultraso ́nicos y en el nu ́mero de elementos piezoel ́ectrico de los transductores ultras ́onicos, generando un aumento significativo en la versatilidad y calidad de estas tecnolog ́ıas. Dentro de estas nuevas t ́ecnicas encontramos la microscop ́ıa de localizaci ́on por ultrasonido (ULM) o su ́per-resoluci ́on ultras ́onica. Esta revolucionaria t ́ecnica es capaz de superar el l ́ımite de difracci ́on y producir una resoluci ́on diez veces mayor en comparaci ́on con la ecograf ́ıa convencional. Puede ser usada para producir ima ́genes vasculares con una resoluci ́on sin precedentes de hasta 5 μm permitiendo as ́ı la visualizaci ́on de vasos sangu ́ıneos microsc ́opicos que hasta ahora no pueden ser vistos por ninguna t ́ecnica disponible cl ́ınicamente. ULM utiliza microburbujas (MBs) de gas (1 μm de di ́ametro) que actu ́an como fuentes acu ́sticas estoc ́asticas. Las MBs se inyectan en el torrente sangu ́ıneo y fluyen dentro del sistema circulatorio, donde aparecen y desaparecen de la regi ́on de inter ́es, lo que permite su localizaci ́on. Luego, la imagen de su ́per-resoluci ́on se construye a partir de la acumulaci ́on de cientos de miles de MBs localizadas.
Actualmente, la mayor parte de la investigaci ́on en ULM se realiza desde el punto de vista de las ciencias de la ingenier ́ıa, que deja a veces a la ciencia fundamental como un aspecto secundario. Nuestro equipo, debido al car ́acter transdisciplinario de esta propuesta, esta constituido por investigadores de el ́area de la ingenier ́ıa, f ́ısica, biomedicina y matem ́aticas. Basados en las fortalezas de este equipo, proponemos estudiar esta tecnolog ́ıa desde la perspectiva de la ciencia fundamental, buscando limitaciones en ella, y estableciendo los mecanismos fisiol ́ogicos que se manifiestan a nivel de las im ́agenes de su ́per-resoluci ́on, permitiendo superar sus actuales limitaciones y potenciando su posible aplicaci ́on en el ́area m ́edica. En este contexto buscaremos como segundo objetivo el visualizar la microvasculatura de muestras de placenta ex-vivo, las que ser ́an donadas voluntariamente por pacientes del hospital regional de Rancagua, y complementar estas observaciones con par ́ametros funcionales y moleculares, con el fin de modelar desde distintas perspectivas nuevos marcadores de funci ́on vascular.
Usualmente para lograr el avance en le desarrollo de este tipo de t ́ecnicas, se requieren condiciones experimentales altamente controlables, las que se logran utilizando sistemas que imitan el tejido en cuesti ́on, el que en nuestro caso es el sistema vascular. Para esto, se utilizan mayormente experimentos in-vitro fabricados a partir de microtubos de 50−150 μm de di ́ametro interno. Sin embargo, existe una gran diferencia entre las propiedades de este tipo de sistemas y las propiedades acu ́sticas de tejido in-vivo humano. Lo que requiere una gran cantidad de iteraciones experimentales retazando el desarrollo. As ́ı, al utilizar tejido humano ex-vivo pretendemos aumentar significativamente la velocidad de la curva de aprendizaje y por consiguiente lograr im ́agenes de su ́per-resoluci ́on humano compatibles dentro de la duraci ́on de esta propuesta. As ́ı mismo, el desarrollo de esta propuesta en un modelo vascular como la placenta humana representa un clara oportunidad para aportar en un ́area actualmente limitada en su capacidad diagn ́ostica, lo que restringe la aplicaci ́on de intervenciones efectivas durante el embarazo, con consecuencias en la salud de la madre y su progenie.
Como proyecciones de este esquema colaborativo esperamos tener acceso a par ́ametros biol ́ogicos con los cuales generar nuevas formas de diagn ́ostico de alta precisi ́on, en especial a nivel de las estructuras involucradas, en primera instancia, con el desarrollo de alteraciones vasculares (i.e. vasos de pequen ̃o calibre). Con ello buscamos desarrollar un tecnolog ́ıa con base cient ́ıfica a trav ́es de la cual ser ́a posible obtener indicadores de mayor sensibilidad y especificidad para variadas condiciones, enfermedades o s ́ındromes, relacionados con la funci ́on vascular.