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BACKGROUND Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterized by dysregulated growth of pulmonary vascular cells and inflammation. A prevailing view is that abnormal cellular metabolism, notably aerobic glycolysis that increases glucose demand, underlies the pathogenesis of PAH. Increased lung glucose uptake(More)
Severe forms of hypertension are characterized by high blood pressure combined with end organ damage. Through the development and refinement of a transgenic rat model of malignant hypertension incorporating the mouse renin gene, we previously identified a quantitative trait locus on chromosome 10, which affects malignant hypertension severity and morbidity.(More)
RATIONALE Iron deficiency without anemia is prevalent in patients with idiopathic pulmonary arterial hypertension and associated with reduced exercise capacity and survival. OBJECTIVES We hypothesized that iron deficiency is involved in the pathogenesis of pulmonary hypertension and iron replacement is a possible therapeutic strategy. METHODS AND(More)
Transgenic rats with inducible expression of the mouse Ren2 gene were used to elucidate mechanisms leading to the development of hypertension and renal injury. Ren2 transgene activation was induced by administration of a naturally occurring aryl hydrocarbon, indole-3-carbinol (100 mg/kg/day by gastric gavage). Blood pressure and renal parameters were(More)
There is considerable interest in the role of iron homeostasis in pulmonary hypertension. Iron supplementation has been reported to ameliorate, and iron chelation to augment, the rise in pulmonary artery pressure seen in healthy volunteers on exposure to altitude. Several independent clinical centers have observed that iron deficiency without anemia is(More)
Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling characterized by dysregulated growth of pulmonary vascular cells and inflammation. In the search for new medicines, the focus is moving toward therapies targeting these mechanisms, drawing on approved oncology interventions, such as tyrosine kinase inhibitors (eg,(More)
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