Vascular Endothelial Growth Factor-A Is Associated with Chronic Mountain Sickness in the Andean Population

Espinoza, J.R.; Alvarez, Giancarlo; León‐Velarde, Fabiola; Preciado, Hugo F. Ju; Macarlupú, José Luis; Rivera-Ch, María; Rodríguez, Jorge; Favier, Judith; Gimenez-Roqueplo, Anne-Paule; Richalet, Jean‐Paul

doi:10.1089/ham.2013.1121

Cited by 15 publications

(15 citation statements)

References 40 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is an important observation since physiologically a lower expression of this gene supposes an enhanced erythropoietic activity. Also recently, a polymorphic variant of the VEGF-A gene was reported to be associated with CMS (Espinoza et al, 2014 ), indicating a possible genetic basis for vascular differences between CMS patients and healthy highlanders. These are still very early but encouraging findings in the linkage of specific genes to the presence and development of EE and CMS.…”

Section: What Causes Cms?mentioning

confidence: 96%

Chronic Mountain Sickness: Clinical Aspects, Etiology, Management, and Treatment

Villafuerte

Corante

2016

High Altitude Medicine & Biology

179

154

View full text Add to dashboard Cite

Villafuerte, Francisco C., and Noemí Corante. Chronic mountain sickness: clinical aspects, etiology, management, and treatment. High Alt Med Biol. 17:61–69, 2016.—Millions of people worldwide live at a high altitude, and a significant number are at risk of developing Chronic Mountain Sickness (CMS), a progressive incapacitating syndrome caused by lifelong exposure to hypoxia. CMS is characterized by severe symptomatic excessive erythrocytosis (EE; Hb ≥19 g/dL for women and Hb ≥21 g/dL for men) and accentuated hypoxemia, which are frequently associated with pulmonary hypertension. In advanced cases, the condition may evolve to cor pulmonale and congestive heart failure. Current knowledge indicates a genetic predisposition to develop CMS. However, there are important risk factors and comorbidities that may trigger and aggravate the condition. Thus, appropriate medical information on CMS is necessary to provide adequate diagnosis and healthcare to high-altitude inhabitants. After reviewing basic clinical aspects of CMS, including its definition, diagnosis, and common clinical findings, we discuss aspects of its etiology, and address its epidemiology, risk factors, and treatment.

show abstract

Section: What Causes Cms?mentioning

confidence: 96%

Chronic Mountain Sickness: Clinical Aspects, Etiology, Management, and Treatment

Villafuerte

Corante

2016

High Altitude Medicine & Biology

179

154

View full text Add to dashboard Cite

show abstract

“…The disease may appear during early adulthood, and turn into a highly prevalent condition mainly in men over 40 years old and in post-menopausal women. The clinical status becomes progressively incapacitating with cardiovascular complications, leading to social exclusion and psychological degradation (León-Velarde et al, 2003; León-Velarde et al, 2005; Richalet et al, 2008; Espinoza et al, 2014; Villafuerte and Corante, 2016). CMS shows a unique worldwide prevalence pattern in native high-altitude dwellers.…”

Section: Introductionmentioning

confidence: 99%

The Genetic Architecture of Chronic Mountain Sickness in Peru

et al. 2019

Self Cite

View full text Add to dashboard Cite

Chronic mountain sickness (CMS) is a pathological condition resulting from chronic exposure to high-altitude hypoxia. While its prevalence is high in native Andeans (>10%), little is known about the genetic architecture of this disease. Here, we performed the largest genome-wide association study (GWAS) of CMS (166 CMS patients and 146 controls living at 4,380 m in Peru) to detect genetic variants associated with CMS. We highlighted four new candidate loci, including the first CMS-associated variant reaching GWAS statistical significance (rs7304081; P = 4.58 × 10 −9 ). By looking at differentially expressed genes between CMS patients and controls around these four loci, we suggested AEBP2 , CAST , and MCTP2 as candidate CMS causal genes. None of the candidate loci were under strong natural selection, consistent with the observation that CMS affects fitness mainly after the reproductive years. Overall, our results reveal new insights on the genetic architecture of CMS and do not provide evidence that CMS-associated variants are linked to a strong ongoing adaptation to high altitude.

show abstract

“…Angiogenesis might be a compensatory process in high-altitude residents that occurs to alleviate hypoxia in microcirculation and it may also be involved in the pathophysiology of CMS (Appenzeller et al, 2003;Ge et al, 2011;Buroker et al, 2012Buroker et al, , 2013Espinoza et al, 2014). The bone marrow is the primary site of angiogenesis and is a readily accessible tissue for the investigation of angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

The Local HIF-2α/EPO Pathway in the Bone Marrow is Associated with Excessive Erythrocytosis and the Increase in Bone Marrow Microvessel Density in Chronic Mountain Sickness

Cui

et al. 2015

High Altitude Medicine & Biology

View full text Add to dashboard Cite

. The local HIF-2a/EPO pathway in the bone marrow is associated with excessive erythrocytosis and the increase in bone marrow microvessel density in chronic mountain sickness. High Alt Med Biol. 16:318-330, 2015.-Aim: Chronic mountain sickness (CMS) is characterized by excessive erythrocytosis, and angiogenesis may be involved in the pathogenesis of this disease. The bone marrow niche is the primary site of erythropoiesis and angiogenesis. This study was aimed at investigating the associations of the levels of hypoxia-inducible factors (HIFs), erythropoietin (EPO), and erythropoietin receptor (EPOR), as well as microvessel density (MVD) in the bone marrow with CMS. Results: A total of 34 patients with CMS and 30 control subjects residing in areas at altitudes of 3000-4500 m were recruited for this study. The mRNA and protein expression of HIF-2a and EPO in the bone marrow cells was significantly higher in the CMS patients than in the controls. Moreover, changes in HIF-2a expression in CMS patients were significantly correlated with EPO and hemoglobin levels. In contrast, the expression of mRNA and protein expression of HIF-1a and EPOR did not differ significantly between the CMS and control patients. Increased MVD was observed in the bone marrow of the patients with CMS and it was significantly correlated with hemoglobin. Conclusions: Bone marrow cells of CMS patients may show enhanced activity of the HIF-2a/EPO pathway, and EPO may regulate the erythropoiesis and vasculogenesis through autocrine or/and paracrine mechanisms in the bone marrow niche. The increased MVD in the bone marrow of CMS patients appears to be involved in the pathogenesis of this disease.

show abstract

Vascular Endothelial Growth Factor-A Is Associated with Chronic Mountain Sickness in the Andean Population

Cited by 15 publications

References 40 publications

Chronic Mountain Sickness: Clinical Aspects, Etiology, Management, and Treatment

Chronic Mountain Sickness: Clinical Aspects, Etiology, Management, and Treatment

The Genetic Architecture of Chronic Mountain Sickness in Peru

The Local HIF-2α/EPO Pathway in the Bone Marrow is Associated with Excessive Erythrocytosis and the Increase in Bone Marrow Microvessel Density in Chronic Mountain Sickness

Contact Info

Product

Resources

About