Emilio A Herrera

Emilio A Herrera
University of Chile · Instituto de Ciencias Biomédicas (ICBM)

DVM, PhD

About

158
Publications
20,667
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Introduction
My research is focused on vascular function in physiological and pathological conditions. I have mainly investigated pathological and adaptive mechanisms related to hypoxia and oxidative stress. In the last decade, I have explored the immediate- mediate- and long-lasting effects (cardiovascular, respiratory and neurological). Using an integrative approach at the organism, isolated organ, cellular and molecular levels, my Laboratory is studying the mechanisms involved for proposing treatments.
Additional affiliations
December 2010 - June 2022
University of Chile
Position
  • University of Santiago, Chile
Description
  • Full Professor Head of Research Laboratory of Vascular Function & Reactivity
September 2007 - November 2010
University of Cambridge
Position
  • Research Associate
June 2007 - present
University of Chile
Position
  • Professor (Assistant)

Publications

Publications (158)
Article
Full-text available
Introducción: La restricción del crecimiento fetal (RCF) se define como la disminución patológica de la tasa de crecimiento fetal, generalmente asociada a insuficiencia placentaria. Se diagnostica mediante ultrasonografía obstétrica y velocimetría Doppler, pero no existe un consenso global respecto a los parámetros referenciados. Objetivo: Brindar...
Article
Full-text available
Neonatal pulmonary hypertension (NPHT) is produced by sustained pulmonary vasoconstriction and increased vascular remodeling. Soluble guanylyl cyclase (sGC) participates in signaling pathways that induce vascular vasodilation and reduce vascular remodeling. However, when sGC is oxidized and/or loses its heme group, it does not respond to nitric oxi...
Article
Full-text available
More than 80 million people live and work (in a chronic or intermittent form) above 2500 masl, and 35 million live in the Andean Mountains. Furthermore, in Chile, it is estimated that 100,000 people work in high-altitude shifts, where stays in the lowlands are interspersed with working visits in the highlands. Acute exposure to high altitude has be...
Article
Full-text available
High altitude hypoxia is a condition experienced by diverse populations worldwide. In addition, several jobs require working shifts where workers are exposed to repetitive cycles of hypobaric hypoxia and normobaric normoxia. Currently, few is known about the biomechanical cardiovascular responses of this condition. In the present study, we investig...
Article
Background Fetal chronic hypoxia is associated with blood flow redistribution and oxidative damage in the brain, leading to increased perinatal morbimortality. Melatonin reduces oxidative stress, improves vascular function, and has neuroprotective effects. Objectives This study aimed to determine the effects of an oral melatonin treatment to pregn...
Article
Full-text available
Calcium signaling is key for the contraction, differentiation, and proliferation of pulmonary arterial smooth muscle cells. Furthermore, calcium influx through store-operated channels (SOCs) is particularly important in the vasoconstrictor response to hypoxia. Previously, we found a decrease in pulmonary hypertension and remodeling in normoxic newb...
Article
Full-text available
An estimated human population of 170 million inhabit at high-altitude (HA, above 2,500 m). The potential pathological effects of HA hypobaric hypoxia during gestation have been the focus of several researchers around the world. The studies based on the Himalayan and Central/South American mountains are particularly interesting as these areas accoun...
Article
Full-text available
Pulmonary arterial hypertension of newborns (PAHN) constitutes a critical condition involving both severe cardiac remodeling and right ventricle dysfunction. One main cause of this condition is perinatal hypoxia and oxidative stress. Thus, it is a public health concern for populations living above 2500 m and in cases of intrauterine chronic hypoxia...
Article
Full-text available
Adopting an integrative approach, by combining studies of cardiovascular function with those at cellular and molecular levels, this study investigated whether maternal treatment with melatonin protects against programmed cardiovascular dysfunction in the offspring using an established rodent model of hypoxic pregnancy. Wistar rats were divided into...
Article
Full-text available
Fetal chronic hypoxia leads to intrauterine growth restriction (IUGR), which is likely to reduce oxygen delivery to the brain and induce long-term neurological impairments. These indicate a modulatory role for oxygen in cerebrovascular development. During intrauterine hypoxia, the fetal circulation suffers marked adaptations in the fetal cardiac ou...
Article
Full-text available
The present study involves experiments and modeling aimed at characterizing the passive structural mechanical behavior of the chronic hypoxic lamb thoracic aorta, whose gestation, birth and postnatal period were carried at high altitude (3600 masl). To this end, the mechanical response was studied via tensile and pressurization tests. The tensile a...
Article
Full-text available
Stroke is the second leading cause of death worldwide, estimated that 1/6 of the world population will suffer it once in their life. The most common type of this medical condition is the ischemic stroke (IS), produced by a thrombotic or embolic occlusion of a major cerebral artery or its branches, leading to the formation of a complex infarct regio...
Article
Full-text available
Background In the fetus, the appropriate balance of prooxidants and antioxidants is essential to negate the detrimental effects of oxidative stress on lung maturation. Antioxidants improve respiratory function in postnatal life and adulthood. However, the outcomes and biological mechanisms of antioxidant action in the fetal lung are unknown. Metho...
Article
Full-text available
In order to reliably assess the rupture-risk of the aorta – along with the hazardousness index of cardiovascular diseases or other extreme conditions, and the effect of possible treatments – it is necessary to know the damage mechanisms that lead to it. In this work, the mechanical damage of hypoxic aortic tissue is characterized, numerically predi...
Article
Pulmonary arterial hypertension of the newborn (PAHN) is a syndrome caused by chronic hypoxia, characterized by decreased vasodilator function, a marked vasoconstrictor activity, proliferation of smooth muscle cells (SMC) and thickening of the extracellular matrix in the pulmonary circulation, among other characteristics. Prostaglandins are derived...
Article
In this work, a novel numerical-experimental procedure is proposed, through the use of the Cardiac Simulation Test (CST), device that allows the exposure of the arterial tissue to in-vitro conditions, mimicking cardiac cycles generated by the heart. The main goal is to describe mechanical response of the arterial wall under physiological conditions...
Preprint
Full-text available
ABSTRACT: In order to reliably assess the rupture-risk of the aorta-along with the hazardousness index of cardiovascular diseases or other extreme conditions, and the effect of possible treatments-it is necessary to know the damage mechanisms that lead to it. In this work, the mechanical damage of hypoxic aortic tissue is characterized, numerically...
Article
Full-text available
RESUMEN Para evaluar de manera fidedigna el riesgo de ruptura de la aorta – junto a los índices de peligrosidad de enfermedades cardiovasculares u otras condiciones extremas y los efectos de posibles tratamientos – se requiere conocer los mecanismos de daño que conducen a ésta. En este trabajo, se caracteriza el daño mecánico del tejido aórtico en...
Article
Full-text available
In this study, we assessed the effects of Atrial Natriuretic Peptide (ANP) and Cinaciguat, as experimental medicines to treat neonatal lambs exposed to chronic hypoxic conditions. To compare the different treatments, the mechanical responses of aorta, carotid, and femoral arterial walls were analyzed by means of axial pre-stretch and ring-opening t...
Article
Full-text available
The hypoxic fetus is at greater risk of cardiovascular demise during a challenge, but the reasons behind this are unknown. Clinically, progress has been hampered by the inability to study the human fetus non-invasively for long period of gestation. Using experimental animals, there has also been an inability to induce gestational hypoxia while reco...
Article
Full-text available
Chronic hypoxia is a condition that increases the cardiovascular complications of newborns gestated and born at high altitude (HA), over 2,500 m above sea level (masl). A particularly complex pathology is pulmonary arterial hypertension of the neonate (PHN), which is increased at HA due to hypobaric hypoxia. Basic and clinical research have recogni...
Article
Full-text available
Chronic hypoxia during gestation induces greater occurrence of perinatal complications such as intrauterine growth restriction, fetal hypoxia, newborn asphyxia, and respiratory distress, among others. This condition may also cause a failure in the transition of the fetal to neonatal circulation, inducing pulmonary arterial hypertension of the neona...
Article
Full-text available
Research using wild animals has diverse aims, such as conservation, environmental management, and the generation of knowledge. The aim of the Institutional Animal Care and Use Committees (IACUCs) is to assure that such research is carried out under high bioethical and animal welfare standards, minimizing animal suffering and environmental impact. T...
Article
Most mammals have a poor tolerance to hypoxia, and prolonged O 2 restriction can lead to organ injury, particularly during fetal and early postnatal life. Nevertheless, the llama (Lama Glama) has evolved efficient mechanisms to adapt to acute and chronic perinatal hypoxia. One striking adaptation is the marked peripheral vasoconstriction measured i...
Article
Full-text available
Prenatal glucocorticoid overexposure has been shown to programme adult cardiovascular function in a range of species, but much less is known about the long-term effects of neonatal glucocorticoid overexposure. In horses, prenatal maturation of the hypothalamus–pituitary–adrenal axis and the normal prepartum surge in fetal cortisol occur late in ges...
Article
Full-text available
Pulmonary arterial hypertension of the neonate (PAHN) is a pathophysiological condition characterized by maladaptive pulmonary vascular remodeling and abnormal contractile reactivity. This is a multifactorial syndrome with chronic hypoxia and oxidative stress as main ethiological drivers, and with limited effectiveness in therapeutic approaches. Me...
Conference Paper
Full-text available
Introduction: Intermittent hypobaric hypoxia (IHH) is a new relative form of human exposure to high altitude. In Chile, 60000 workers who live at sea level must shift every 5 or 7 days to work in mining prospecting located over 3000 MASL. Pathophysiological effects of chronic and acute hypobaria in humans have been studied extensively and are close...
Article
Extensive periods of hypoxic cause adaptive changes that make it possible to respond to the demands imposed by the environment. However, there are cases where this exposure is intermittent, as is the case of workers in andean areas. The objective of this communication was to verify the morphological and mechanical effects on diaphragm and lungs of...
Article
Full-text available
Cardiovascular risk associated with fetal growth restriction (FGR) could result from an early impaired vascular function. However, whether this effect results in premature vascular aging has not been addressed. We studied the ex vivo reactivity of carotid and femoral arteries in fetal (near term), adults (eight months-old) and aged (16 months-old)...
Article
Full-text available
Neonatal lambs, as other neonates, have physiologically a very low plasma melatonin concentration throughout 24 h. Previously, we found that melatonin given to neonates daily for 5 days decreased heart weight and changed plasma cortisol and gene expression in the adrenal and heart. Whether these changes could compromise the responses to life challe...
Article
Full-text available
Aim: Fetal growth restriction (FGR) is associated with endothelial dysfunction and cardiovascular diseases in adult subjects. Early vascular remodelling and epigenetic changes occurring on key endothelial genes might precede this altered vascular function. Further, it has been proposed that oxidative stress during development may determine some of...
Article
Nitric oxide (NO) is the main vasodilator agent that drives the rapid decrease of pulmonary vascular resistance for the respiratory onset during the fetal to neonatal transition. Nevertheless, the enhanced NO generation by the neonatal pulmonary arterial endothelium does not prevent development of hypoxic pulmonary hypertension in species without a...
Article
Full-text available
Background: Living above 2,500 meters in hypobaric conditions induces pulmonary arterial hypertension of the neonate (PAHN), a syndrome whose main features are: pathological remodeling of the pulmonary vessels, abnormal vascular reactivity and increased oxidative stress. Melatonin could have pulmonary antioxidant, anti-remodeling and vasodilating...
Article
Full-text available
Chronic hypobaric hypoxia during fetal and neonatal life induces neonatal pulmonary hypertension. Hypoxia and oxidative stress are driving this condition, which implies an increase generation of reactive oxygen species (ROS) and/or decreased antioxidant capacity. Melatonin has antioxidant properties that decrease oxidative stress and improves pulmo...
Article
Full-text available
Evidence derived from human clinical studies and experimental animal models shows a causal relationship between adverse pregnancy and increased cardiovascular disease in the adult offspring. However, translational studies isolating mechanisms to design intervention are lacking. Sheep and humans share similar precocial developmental milestones in ca...
Data
Raw data. Complying with data policy, Excel spreadsheet files are provided with the underlying numerical data points for all graphs contained within the manuscript. (XLSX)
Data
Placental measurements. Measurements at 138 dGA: A, total placentome weight; B, placentome distribution; and C, fetal:placentome weight ratio. Values are mean ± SEM. Groups are N (open symbols, n = 12), H (grey symbols, n = 8), HC (red symbols, n = 9), and NC (blue symbols, n = 9). There are no significant differences between groups. dGA, days of g...
Article
Full-text available
CONEI, D.; DEL SOL, M.; MUÑOZ, R.; ESCOBAR, C. M.; SAAVEDRA, H.; HERRERA, E. A. & GARCÍA-HERRERA, C. M. Efectos morfológicos y mecánicos en ratas Sprague Dawley sometidas a ciclos de hipoxia. Int. J. Morphol., 37(3):908-911, 2019. RESUMEN: Periodos extensos de hipoxia provocan cambios adaptativos que permiten responder a las demandas impuestas por...
Article
Over 30 years ago Sir David Barker first proposed the theory that events in early life could explain an individuals' risk of non-communicable disease in later life; the Developmental Origins of Health and Disease (DOHaD) theory. During the 1990s the validity of the DOHaD theory was extensively tested in a number of human populations and the mechani...
Article
Intrauterine growth restriction (IUGR) is a common obstetric complication with immediate and life-long consequences for offspring health. Yet the mechanisms underlying its aetiology require elucidation. Recent work in the guinea pig shows that progressive uterine artery occlusion induced IUGR and vascular dysfunction in pups. Here we explore the ex...
Article
Experimental studies that are relevant to human pregnancy rely on the selection of appropriate animal models as an important element in experimental design. Consideration of the strengths and weaknesses of any animal model of human disease is fundamental to effective and meaningful translation of preclinical research. Studies in sheep have made sig...
Article
Full-text available
Fetal growth restriction (FGR) is a perinatal condition associated with a low birth weight that results mainly from maternal and placental constrains. Newborns affected by this condition are more likely to develop in the long term cardiovascular diseases whose origins would be in an altered vascular structure and function defined during fetal devel...
Article
Full-text available
The pulmonary arteries are exquisitely responsive to oxygen changes. They rapidly and proportionally contract as arterial PO2 decrease, and they relax as arterial PO2 is re-established. The hypoxic pulmonary vasoconstriction (HPV) is intrinsic since it does not require neural or endocrine factors, as evidenced in isolated vessels. On the other hand...
Article
Full-text available
Over 30 years ago Sir David Barker first proposed the theory that events in early life could explain an individuals’ risk of non‐communicable disease in later life; the Developmental Origins of Health and Disease (DOHaD) theory. During the 1990s the validity of the DOHaD theory was extensively tested in a number of human populations and the mechani...
Article
Full-text available
Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN), a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the funct...
Article
Full-text available
More than 140 million people live and works (in a chronic or intermittent form) above 2500 m worldwide and 35 million live in the Andean Mountains. Furthermore, in Chile, it is estimated that 55,000 persons work in high altitude shifts, where stays at lowlands and interspersed with working stays at highlands. Acute exposure to high altitude has bee...
Article
Full-text available
Key points: Perinatal hypoxia causes pulmonary hypertension in neonates, including humans. However, in species adapted to hypoxia, such as the llama, there is protection against pulmonary hypertension. Nitric oxide (NO) is a vasodilatator with an established role in the cardiopulmonary system of many species, but its function in the hypoxic pulmon...
Article
Full-text available
Alterations in cardiac energy metabolism play a key role in the pathogenesis of diabetic cardiomyopathy. Hypercholesterolemia associated with bioenergetic impairment and oxidative stress has not been well characterized in the cardiac function under glycemic control deficiency conditions. This work aimed to determine the cardioprotective effects of...
Data
Supplementary Figure 1: ezetimibe protects againts the increase on total cholesterol in plasma, cholesterol content in heart and heart weight induced by a high cholesterol diet. In rats fed for 4 weeks with control, diet (C), high cholesterol diet (HC) or high cholesterol diet containing 0.001% ezetimibe (HCE) the A) total cholesterol in plasma, B)...
Conference Paper
Full-text available
Neonatal pulmonary hypertension (NPH) is a condition characterized by vascular remodeling and abnormal vascular reactivity. This is a multifactorial syndrome with a limited efficacy in current therapeutic approaches, with chronic hypoxia and oxidative stress as major determining factors of pulmonary vascular dysfunction (1). Melatonin is a neurohor...
Article
Full-text available
Aim: Fetal growth restriction (FGR) is associated with a variety of cardiometabolic diseases in adulthood which could involve remodeling processes of the vascular walls that could start in the fetal period. However, there is no consensus whether this remodeling affects in a similar way the whole vascular system. We aimed to determine the effects of...
Article
Full-text available
Marfan syndrome (MFS) is a genetic disorder that affects connective tissue, impairing cardiovascular structures and function, such as heart valves and aorta. Thus, patients with Marfan disease have a higher risk of developing circulatory problems associated with mitral and aortic valves prolapse, manifested as dilated aorta and aortic aneurysm. How...
Article
Key points: Chronic fetal hypoxaemia is a common pregnancy complication associated with intrauterine growth restriction that may influence respiratory outcome at birth. We investigated the effect of maternal chronic hypoxia for a month in late gestation on signalling pathways regulating fetal lung maturation and the transition to air-breathing at...
Chapter
Most of the worldwide deaths in patients with non-communicable diseases are due to cardiovascular and metabolic diseases, which are determined by a mix of environmental, genetic and epigenetic factors, and by their interactions. The aetiology of most cardiovascular diseases has been partially linked with in utero adverse conditions that may increas...
Data
Full-text available