Peripheral blood mononuclear cell gene expression in healthy adults rapidly transported to high altitude

Nicole M Herman,1 Diane E Grill,2 Paul J Anderson,1 Andrew D Miller,1 Jacob B Johnson,1 Kathy A O’Malley,1 Maile L Ceridon Richert,1 Bruce D Johnson1 1Department of Cardiovascular Diseases, 2Department of Biostatistics, Mayo Clinic Rochester, MN, USA Abstract: Although mechanisms of high altitude illness have been studied extensively, the processes behind the development of these conditions are still unclear. Few genome-wide studies on rapid exposure to high altitude have been performed. Each year, scientists and support workers are transferred by plane from McMurdo Station in Antarctica (sea level) to the Amundsen-Scott South Pole Station at 2,835 meters. This uniform and rapid transfer to altitude provides a unique opportunity to study the effects of hypobaric hypoxia on gene expression that may help illustrate the body's adaptations to these conditions. We hypothesized that an extensive number of genes would change with rapid exposure to altitude and further expected that these genes would correspond to inflammatory pathways proposed as a mechanism in development of acute mountain sickness. Peripheral venous blood samples were drawn from 98 healthy subjects at sea level and again on day two at altitude. Microarray analysis was performed on these samples. In total, 1,118 probe sets with significant P-values and fold changes (90% upregulated) were identified and entered into MetaCore™ software. Several pathways, including oxidative phosphorylation, cytoskeleton remodeling, and platelet aggregation, were significantly represented by the data set and all were upregulated. Many genes changed expression, and the vast majority of these increased. Increased metabolism in peripheral blood mononuclear cells suggests increased inflammatory activity. Keywords: peripheral blood mononuclear cells, microarray, gene expression, acute mountain sicknes

Obstructive Ventilatory Disorder in Heart Failure—Caused by the Heart or the Lung?

Heart failure (HF) is a clinical syndrome frequently associated with airway obstruction, either as a respiratory comorbidity or as a direct consequence of HF pathophysiology. Recognizing the relative contribution of an underlying airway disease as opposed to airway obstruction due to volume overload and left atrial pressure elevation is of importance for the appropriate management of patients affected by HF. This review focuses on “les liaisons dangereuses” between the heart and the lungs, outlying recent advances linking in a vicious circle of chronic obstructive lung disease (COPD) and obstructive sleep apnea (OSA) on one side and HF on the other side. It also discusses the role of pivotal diagnostic tools such as pulmonary function tests and cardiopulmonary exercise test to determine the contribution of HF and COPD to symptoms and clinical status. Treatment implications are discussed as well.SCOPUS: re.jinfo:eu-repo/semantics/publishe