SNPs, linkage disequilibrium, and chronic mountain sickness in Tibetan Chinese.

Chronic mountain sickness (CMS) is estimated at 1.2% in Tibetans living at the Qinghai-Tibetan Plateau. Eighteen single-nucleotide polymorphisms (SNPs) from nine nuclear genes that have an association with CMS in Tibetans have been analyzed by using pairwise linkage disequilibrium (LD).

Opioid receptors mediate enhancement of ACh-induced aorta relaxation by chronic intermittent hypobaric hypoxia.

The present study was designed to investigate the role of opioid receptors in the vasorelaxation effect of chronic intermittent hypobaric hypoxia (CIHH) in thoracic aorta rings and the underlying mechanism in rats. Adult male Sprague-Dawley (SD) rats were randomly divided into 2 groups: CIHH treatment group and control group. The rats in CIHH group were exposed to hypoxia in a hypobaric chamber (simulated 5 000 m altitude) for 28 days, 6 h per day.

Beneficial effects of intermittent hypobaric hypoxia on the body.

Myocardial ischemia and reperfusion (I/R) is a common problem in clinic and there is no satisfactory method for prevention or treatment of I/R injury so far. Chronic intermittent hypobaric hypoxia (CIHH), similar to the concept of ischemia preconditioning (IPC)or altitude hypoxia adaptation (AHA), has been recognized to confer a protective effect on heart against I/R injury with a longer protective effect than IPC and a less adverse effect than AHA. It has been proved that CIHH increases myocardial tolerance to ischemia or hypoxia, reserving cardiac function and preventing arrhythmia during I/R.

VEGFA SNPs and transcriptional factor binding sites associated with high altitude sickness in Han and Tibetan Chinese at the Qinghai-Tibetan Plateau.

Mountain sickness (MS) occurs among humans visiting or inhabiting high altitude environments. We conducted genetic analyses of seven single nucleotide polymorphisms (SNPs) in the promoter region of VEGFA gene for lowland (Han) and highland (Tibetan) Chinese. The seven SNPs were evaluated in Han and Tibetan patients with acute (A) and chronic (C) MS.

Prolyl hydroxylase domain protein 2 regulates the intracellular cyclic AMP level in cardiomyocytes through its interaction with phosphodiesterase 4D.

Cyclic adenosine 3',5'-monophosphate (cAMP), which is synthesized by adenylyl cyclase (AC) and degraded by phosphodiesterase (PDE), plays crucial roles in the regulation of multiple cellular functions and physiological processes. Prolyl hydroxylase domain (PHD) proteins, which belong to a family of dioxygenases that function as oxygen sensors through their hydroxylation activity, have been implicated in multiple signaling pathways. Here, we aimed to determine whether PHD played a role in regulating intracellular cAMP level in cardiomyocytes.

Hypobaric intermittent hypoxia attenuates hypoxia-induced depressor response.

Background: Hypobaric intermittent hypoxia (HIH) produces many favorable effects in the cardiovascular system such as anti-hypertensive effect. In this study, we showed that HIH significantly attenuated a depressor response induced by acute hypoxia.

Methodology/principal Findings: Sprague-Dawley rats received HIH in a hypobaric chamber simulating an altitude of 5000 m.

AKT3, ANGPTL4, eNOS3, and VEGFA associations with high altitude sickness in Han and Tibetan Chinese at the Qinghai-Tibetan Plateau.

Mountain sickness (MS) occurs among humans visiting or inhabiting high altitude environments. We conducted genetic analyses of the AKT3, ANGPTL4, eNOS3 and VEGFA genes in lowland (Han) and highland (Tibetan) Chinese. Ten single nucleotide polymorphisms (SNPs) were evaluated in Han and Tibetan patients with acute (A) and chronic (C) MS.

EPAS1 and EGLN1 associations with high altitude sickness in Han and Tibetan Chinese at the Qinghai-Tibetan Plateau.

High altitude sickness (HAS) occurs among humans visiting or inhabiting high altitude environments. Genetic differences in the EPAS1 and EGLN1 genes have been found between lowland (Han) and highland (Tibetan) Chinese. Three SNPs within EPAS1 and EGLN1 were evaluated in Han and Tibetan patients with acute mountain sickness (AMS) and chronic mountain sickness (CMS).

Mitochondrial energy metabolism plays a critical role in the cardioprotection afforded by intermittent hypobaric hypoxia.

Intermittent hypobaric hypoxia (IHH) is an effective protective strategy against myocardial ischaemia-reperfusion (I/R) injury, but the precise mechanisms are far from clear. To understand the overall effects of IHH on the myocardial proteins during I/R, we analysed functional performance and the protein expression profile in isolated hearts from normoxic rats and from rats adapted to IHH (5000 m, 4 h day(-1), 4 weeks) following I/R injury (30 min/45 min). Intermittent hypobaric hypoxia significantly improved the postischaemic recovery of left ventricular function compared with the recovery in time-matched normoxic control hearts.

Facilitation of chronic intermittent hypobaric hypoxia on carotid sinus baroreflex in anesthetized rats.

Our previous study showed that chronic intermittent hypobaric hypoxia (CIHH) could prevent decreases in systemic arterial blood pressure (SABP) during acute hypoxia. However, the mechanism was not clear. The purpose of the present study was to observe whether the carotid sinus baroreflex (CSB) was involved in the antagonizing effect of CIHH on SABP decrease induced by acute hypoxia and to explore the underlying mechanism using perfusion technique in rat isolated carotid sinus area.

Intermittent hypobaric hypoxia improves postischemic recovery of myocardial contractile function via redox signaling during early reperfusion.

Intermittent hypobaric hypoxia (IHH) protects hearts against ischemia-reperfusion (I/R) injury, but the underlying mechanisms are far from clear. ROS are paradoxically regarded as a major cause of myocardial I/R injury and a trigger of cardioprotection. In the present study, we investigated whether the ROS generated during early reperfusion contribute to IHH-induced cardioprotection.

Proteomic analysis of mitochondrial proteins in cardiomyocytes from rats subjected to intermittent hypoxia.

Intermittent hypoxia (IH) markedly enhances cardiac tolerance against ischemia/reperfusion injury, but its mechanism and molecular basis remain unclear. For exploring the expression of mitochondrial proteins induced by IH, two-dimensional electrophoresis and Thermo Finnigan LTQ mass spectrometer (MS) were applied. After comparing the protein profiles of myocardial mitochondria between IH and normoxic hearts, 14 protein spots were found to be altered more than threefold between the two groups, 11 of which were identified by Finnigan LTQ MS.

[Effect of chronic intermittent hypobaric hypoxia on contractile activity of arteries in rats].

The present study is aimed to investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on contractile activities in isolated thoracic aorta and pulmonary artery rings and the underlying mechanism in rats. Sprague-Dawley (SD) rats were randomly divided into 4 groups: control group (CON), 14 days CIHH treatment group (CIHH14), 28 days CIHH treatment group (CIHH28) and 42 days CIHH treatment group (CIHH42). CIHH rats were exposed to hypoxia in a hypobaric chamber simulating 5 000 m altitude, 6 h daily for 14, 28 and 42 d, respectively.

Therapeutic effect of intermittent hypobaric hypoxia on myocardial infarction in rats.

Intermittent hypobaric hypoxia (IHH) preconditioning protects the heart against ischemic injuries. However, little is known about the therapeutic effect of IHH on myocardial infarction (MI). The aim of this study was to test whether IHH treatment influences infarct size and cardiac performance after MI.

Prolyl hydroxylase 2: a novel regulator of β2 -adrenoceptor internalization.

Adrenergic receptor (AR)-mediated signalling is modulated by oxygen levels. Prolyl hydroxylases (PHDs) are crucial for intracellular oxygen sensing and organism survival. However, it remains to be clarified whether or how PHDs are involved in the regulation of β(2) -adrenoceptor (β(2) -AR) signalling.

[Effects of chronic intermittent hypobaric hypoxia on immune function in rat].

Aim: To elucidate the effect of CIHH on cellular immunity and humoral immunity in rat by using flow cytometry method, immunohistochemistry method and electron microscopy techniques.

Methods: Forty-eight male adult Sprague-Dawley rats were randomly divided into 4 groups: control(CON) group, 14 days CIHH (CIHH14) group, 28 days CIHH (CIHH28) group, 42 days CIHH (CIHH42) group. The animals in CIHH groups were exposed to 14, 28 and 42 days hypobaric hypoxia(simulated 3 000 m altitude, 5 h per day), respectively.

Prolyl hydroxylase 3 interacts with Bcl-2 to regulate doxorubicin-induced apoptosis in H9c2 cells.

Prolyl hydroxylases (PHDs) are dioxygenases that use oxygen as a co-substrate to hydroxylate proline residues. Three PHD isoforms (PHD1, PHD2 and PHD3) have been identified in mammalian cells. PHD3 expression is upregulated in some cardiac diseases such as cardiomyopathy, myocardial ischemia-reperfusion injury and congestive heart failure, all of which are associated with apoptosis.

Genetic associations with mountain sickness in Han and Tibetan residents at the Qinghai-Tibetan Plateau.

Background: Acute (AMS) and chronic (CMS) mountain sicknesses are illnesses that occur among humans visiting or inhabiting high-altitude environments, respectively. Some individuals are genetically less fit than others when stressed by an extreme high-altitude environment. Seven blood physiological parameters and five genetic polymorphisms were studied in Han patients with AMS and Tibetan patients with CMS.

beta2- but not beta1-adrenoceptor activation modulates intracellular oxygen availability.

beta-Adrenoceptors (beta-ARs) play a critical role in the regulation of cardiovascular function. Intracellular oxygen homeostasis is crucial for the survival of cardiomyocytes. However, it is still unclear whether beta-AR activation can modulate intracellular oxygen.

Effects of chronic intermittent hypobaric hypoxia on the L-type calcium current in rat ventricular myocytes.

This study was conducted to investigate the role of the L-type calcium channel in the cardioprotection afforded by chronic intermittent hypobaric hypoxia (CIHH). Rats were exposed to CIHH for 28 days (CIHH28) or 42 days (CIHH42), respectively, before their ventricular myocytes were isolated for electrophysiological studies. Under normal recording conditions, no difference was found in the current density and voltage dependence of activation and inactivation of I(caL) recorded in CIHH28 and CIHH42 myocytes, compared with those in control myocytes isolated from rats exposed to sea-level air.

Inhibition of mitochondrial translocator protein prevents atrial fibrillation.

Atrial fibrillation is the most common arrhythmia encountered in clinical practice. It can cause severe complications such as congestive heart failure and stroke. However, identification of prime targets for efficient therapeutic intervention remains a challenge.

Chronic intermittent hypobaric hypoxia decreases beta-adrenoceptor activity in right ventricular papillary muscle.

Chronic intermittent hypobaric hypoxia (CIHH) has an effective cardiac protection against ischemia-reperfusion injury. However, the underlying mechanisms are not fully known. It has been shown that blockade of beta-adrenergic receptor exerts anti-arrhythmic action and improves cardiac remodeling in ischemic myocardium.

Preservation of TSPO by chronic intermittent hypobaric hypoxia confers antiarrhythmic activity.

Abnormal activation of mitochondrial translocator protein (TSPO) contributes to arrhythmogenesis during cardiac metabolic compromise; however, its role in the antiarrhythmic activities of chronic hypoxia adaptation remains unclear. Our results demonstrated that 80% of normoxic rats developed ischaemic VF, whereas this condition was seldom observed in rats with 14 days of chronic intermittent hypobaric hypoxia (CIHH). TSPO stimulation or inhibition affected the arrhythmias incidence in normoxic rats, but did not change the CIHH-mediated antiarrhythmic effects.

Mitochondrial benzodiazepine receptors mediate cardioprotection of estrogen against ischemic ventricular fibrillation.

The cardioprotective effects of estrogen remain controversial in clinical practice. Previous reports have shown that cardioprotective mechanisms converge on the mitochondria, but the role of mitochondria in estrogen's actions on cardiac arrhythmias is unclear. Here, we report that stimulation or inhibition of mitochondrial benzodiazepine receptors (mBzR) affected ventricular fibrillation (VF) almost in an "all-or-none" manner in an in vitro rat heart model of ischemic VF.