A5085792386- High Altitude and Hypoxia
- Neuroscience of respiration and sleep
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Heart Rate Variability and Autonomic Control
- Heme Oxygenase-1 and Carbon Monoxide
- Cancer, Hypoxia, and Metabolism
- Climate Change and Health Impacts
- Adipose Tissue and Metabolism
- Erythropoietin and Anemia Treatment
- Hemoglobinopathies and Related Disorders
- Cardiovascular and Diving-Related Complications
- Ion channel regulation and function
- Travel-related health issues
- Nitric Oxide and Endothelin Effects
- Cardiovascular and exercise physiology
- Mitochondrial Function and Pathology
- Cardiovascular Health and Risk Factors
- Enzyme function and inhibition
- Cardiac electrophysiology and arrhythmias
- Thermoregulation and physiological responses
- Respiratory Support and Mechanisms
- Metabolomics and Mass Spectrometry Studies
- Hematological disorders and diagnostics
- Exercise and Physiological Responses
- Cardiovascular Health and Disease Prevention
Universidad Peruana Cayetano Heredia
2015-2025
Centro Cardiologico Monzino
2015
IRCCS Istituto Auxologico Italiano
2015
University of Oxford
2007-2013
The Gurdon Institute
2006
The hypoxic conditions at high altitudes present a challenge for survival, causing pressure adaptation. Interestingly, many high-altitude denizens (particularly in the Andes) are maladapted, with condition known as chronic mountain sickness (CMS) or Monge disease. To decode genetic basis of this disease, we sequenced and compared whole genomes 20 Andean subjects (10 CMS 10 without). We discovered 11 regions genome-wide significant differences haplotype frequencies consistent selective...
In contrast to Andean natives, high-altitude Tibetans present with a lower hemoglobin concentration that correlates reproductive success and exercise capacity. Decades of physiological genomic research have assumed the in Himalayan natives results from blunted erythropoietic response hypoxia (i.e., no increase total mass). contrast, herein we test hypothesis is result greater plasma volume, rather than an absence increased production. We assessed mass, volume blood lowlanders at sea level,...
Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. EPAS1 , a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration Tibetans. We provide evidence for an association between adaptive variant (rs570553380) the same phenotype low hematocrit Andean highlanders. This Andean-specific missense present at modest frequency Andeans absent other populations vertebrate species except coelacanth....
Intracellular pH (pH(i)) in heart is regulated by sarcolemmal H(+)-equivalent transporters such as Na(+)-H(+) exchange (NHE) and Na(+)-HCO(3) (-) cotransport (NBC). Inhibition of NBC influences pH(i) can be cardioprotective animal models post-ischaemic reperfusion. Apart from a rabbit polyclonal NBC-antibody, selective inhibitor compound has not been studied. Compound S0859 (C(29)H(24)ClN(3)O(3)S) putative inhibitor. Here, we provide the drug's chemical structure, test its potency...
Blood pressure increases during acute exposure to high altitude in healthy humans. However, little is known on effects hypertensive subjects or the treatment efficacy this condition. Objectives of High Altitude Cardiovascular Research (HIGHCARE)-Andes Lowlanders Study were investigate high-altitude 24-hour ambulatory blood and assess antihypertensive setting. One hundred untreated with mild hypertension (screening pressure, 144.1±9.8 mm Hg systolic, 92.0±7.5 diastolic) randomized...
Corante, Noemí, Cecilia Anza-Ramírez, Rómulo Figueroa-Mujíca, José Luis Macarlupú, Gustavo Vizcardo-Galindo, Grzegorz Bilo, Gianfranco Parati, Jorge L. Gamboa, Fabiola León-Velarde, and Francisco C. Villafuerte. Excessive erythrocytosis cardiovascular risk in Andean highlanders. High Alt Med Biol. 19:221-231, 2018.-Cardiovascular diseases are the main cause of death worldwide. Life under high-altitude (HA) hypoxic conditions is believed to provide highlanders with a natural protection...
Excessive erythrocytosis (EE) is the hallmark of chronic mountain sickness (CMS), a prevalent syndrome in high-altitude Andean populations. Although hypoxemia represents its underlying stimulus, why some individuals develop EE despite having altitude-normal blood erythropoietin (Epo) concentration still unclear. A soluble form Epo receptor (sEpoR) has been identified human and competes directly for with membrane counterpart (mEpoR). Thus, reduced levels circulating sEpoR could lead to higher...
Excessive erythrocytosis (EE; hemoglobin concentration [Hb] ≥21 g/dL in adult males) is associated with increased cardiovascular risk highlander Andeans. We sought to quantify shear stress and assess endothelial function via flow-mediated dilation (FMD) male Andeans without EE. hypothesized that FMD would be impaired EE after accounting for improve isovolemic hemodilution. Brachial artery were assessed 23 (age: 40±15 years [mean±SD]; Hb<21 g/dL) 19 43±14 years; Hb≥21 Cerro de Pasco, Peru...
Abstract Monge’s disease (chronic mountain sickness (CMS)) is a maladaptive condition caused by chronic (years) exposure to high-altitude hypoxia. One of the defining features CMS excessive erythrocytosis with extremely high hematocrit levels. In Andean population, prevalence vastly different between males and females, being rare in females. Furthermore, there sharp increase incidence females after menopause. this study, we assessed role sex hormones (testosterone, progesterone, estrogen)...
High-altitude (HA) hypoxia may alter the structural-functional integrity of neurovascular unit (NVU). Herein, we compared male lowlanders (n = 9) at sea level (SL) and after 14 days acclimatization to 4300 m (chronic HA) in Cerro de Pasco (CdP), Péru (HA), against sex-, age- body mass index-matched healthy highlanders native CdP (lifelong HA). Venous blood was assayed for serum proteins reflecting NVU integrity, addition free radicals nitric oxide (NO). Regional cerebral flow (CBF) examined...
Thomson, Timothy M., Fresia Casas, Harold Andre Guerrero, Rómulo Figueroa-Mujíca, Francisco C. Villafuerte, and Claudia Machicado. Potential protective effect from COVID-19 conferred by altitude: A longitudinal analysis in Peru during full lockdown. High Alt Med Biol. 22: 209–224, 2021.
The beneficial role of erythrocytosis for O2 transport has been questioned by evidence from bloodletting and hemodilution research as well studies suggesting the existence an "optimal" hematocrit (Hct) or hemoglobin concentration ([Hb]) value. To assess to what extent is in Andean men at high altitude, we examined discussed optimal [Hb] using a mathematical approach modeling mixed (mean) venous Po2 (Pv(O2)) arterial content, considering both relation between Po2. Relations other...
Abstract EGLN1 encodes the hypoxia‐inducible factor (HIF) pathway prolyl hydroxylase 2 (PHD2) that serves as an oxygen‐sensitive regulator of HIF activity. The locus exhibits a signature positive selection in Tibetan and Andean populations is associated with hemoglobin concentration Tibetans. Recent reports provide evidence for functional roles protein‐coding variants within first exon (rs186996510, rs12097901) are linked to adaptive signal Tibetans, yet whether these same present contribute...
Rationale: Chronic exposure to hypoxia is associated with elevated sympathetic nervous activity and reduced vascular function in lowlanders, Andean highlanders suffering from excessive erythrocytosis (EE); however, the mechanistic link between chronically hypoxia-induced dysfunction has not been determined. Objective: To determine impact of heightened on resistance artery endothelial-dependent dilation (EDD), endothelial-independent dilation, lowlanders without EE. Methods Results: We tested...
What is the central question of this study? Herein, a methodological overview our research team's (Global REACH) latest high altitude expedition to Peru provided. main finding and its importance? The experimental objectives, organization, measurements key cohort data are discussed. select presented in manuscript demonstrate haematological differences between lowlanders Andeans with without excessive erythrocytosis. also that exercise capacity was similar study groups at altitude. forthcoming...
Orr, Jeremy E., Erica C. Heinrich, Matea Djokic, Dillon Gilbertson, Pamela N. Deyoung, Cecilia Anza-Ramirez, Francisco Villafuerte, Frank L. Powell, Atul Malhotra, and Tatum Simonson. Adaptive servoventilation as treatment for central sleep apnea due to high-altitude periodic breathing in nonacclimatized healthy individuals. High Alt Med Biol. 19:178–184, 2018. Aims: Central (CSA) is common at high altitude, leading desaturation disruption. We hypothesized that noninvasive ventilation using...
Heme oxygenase (HO) enzymes catalyze heme into biliverdin, releasing carbon monoxide (CO) and iron circulation. These byproducts of degradation can have potent cytoprotective effects in the face stressors such as hypoxia ischemia-reperfusion events. The potential for exogenous use CO a therapeutic agent has received increasing attention throughout past few decades. Further, HO are noted putatively adaptive diving mammals certain high-altitude human populations that frequently exposed to...