Slingo ME, Turner PJ, Christian HC, Buckler KJ, Robbins PA. The von Hippel-Lindau Chuvash mutation in mice causes carotidbody hyperplasia and enhanced ventilatory sensitivity to hypoxia. J Appl Physiol 116: 885–892, 2014. First published September 12, 2013; doi:10.1152/japplphysiol.00530.2013.—The hypoxia-inducible factor (HIF) family of transcription factors coordinates diverse cellular and sy...

Aim Hypoxia-inducible factors (HIFs) are O2-sensitive transcription that regulate multiple biological processes which essential for cellular adaptation to hypoxia. Small molecule inhibitors of HIF-prolyl hydroxylase domain (PHD) dioxygenases (HIF-PHIs) activate HIF-dependent transcriptional programs and have broad clinical potential. HIF-PHIs currently in global late-stage development the treat...

In this article, we try to summarize the most important novel biological information on the complex interrelationships between acid-base alterations and hypoxia-inducible factor (HIF) signaling. Extracellular and intracellular acid-base alterations affect HIF signaling in part independently of hypoxia, and involve, among others, effects on cytoprotection and apoptosis. Conversely, HIF signaling...

Patients with single ventricle are often quite ill and present complex management dilemmas. The distribution of blood flow to the systemic and pulmonary circulations, which in this patient population are in parallel rather than series, depends primarily on the relative resistances of the respective vascular beds. The entire cardiac output is managed by the single ventricle and must somehow divi...

AIMS We hypothesized that chronic heart failure as a model of systemic hypoxia may result in systemic inflammation. The signs of a systemic inflammatory response should disappear after successful mechanical circulatory support using biventricular assist device systems. METHODS AND RESULTS Plasma levels of cytokines (IL-6, IL-8, TNF-alpha) and soluble adhesion molecules (sVCAM, sE-, sL-, sP-Se...

Fibrosis, characterized by increased extracellular matrix (ECM) deposition, and widespread vasculopathy, has the prominent trait of chronic hypoxia. Hypoxia inducible factors-1α (HIF-1α), a key transcriptional factor in response to this chronic hypoxia, is involved in fibrotic disease, such as Systemic sclerosis (SSc). The implicated function of HIF-1α in fibrosis include stimulation of excessi...

Adipose tissue metabolism and circulation play an important role in human health. It is well-known that adipose tissue mass is increased in response to excess caloric intake leading to obesity and further to local hypoxia and inflammatory signaling. Acute exercise increases blood supply to adipose tissue and mobilization of fat stores for energy. However, acute exercise during systemic hypoxia ...

BACKGROUND Management strategies for preoperative infants with hypoplastic left heart syndrome (HLHS) include increased inspired nitrogen (hypoxia) and increased inspired carbon dioxide (hypercarbia). There are no studies directly comparing these 2 therapies in humans. This study compares the impact of hypoxia versus hypercarbia on oxygen delivery, under conditions of fixed minute ventilation. ...

Local tissue oxygenation profoundly influences placental development. To elucidate the impact of hypoxia on cellular and molecular adaptation in vivo, pregnant mice at embryonic days 7.5-11.5 were exposed to reduced environmental oxygen (6-7% O2) for various periods of time. Hypoxia-inducible factor (HIF)-1alpha mRNA was highly expressed in the placenta, whereas HIF-2alpha was predominantly fou...

Although the effects of ischemia-reperfusion have received considerable attention, few studies have directly evaluated the microcirculatory response to systemic hypoxia. The overall objective of this study was to assess the effect of environmental hypoxia on adhesive interactions of circulating leukocytes with rat mesenteric venules by using intravital microscopy. Experiments were designed to 1...