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PPARA genetic variants increase the risk for cardiac pumping function reductions following acute high-altitude exposure: A self-controlled study.

ABSTRACT: BACKGROUND:Left cardiac pumping function determines the compensatory capacity of the cardiovascular system following acute high-altitude exposure. Variations in cardiac output (CO) at high altitude are inconsistent between individuals, and genetic susceptibility may play a crucial role. We sought to identify genetic causes of cardiac pumping function variations and describe the genotype-phenotype correlations. METHODS:A total of 151 young male volunteers were recruited and transferred to Lhasa (3,700 m) from Chengdu (<500 m) by plane. Genetic information related to hypoxic signaling and cardiovascular-related pathways was collected before departure. Echocardiography was performed both before departure and 24 hr after arrival at high altitude. RESULTS:Here we reported that PPARA variants were closely related to high-altitude cardiac function. The variants of rs6520015 C-allele and rs7292407 A-allele significantly increased the risk for cardiac pumping function reductions following acute high-altitude exposure. In addition, the individuals carrying haplotypes in PPARA, namely, rs135538 C-allele, rs4253623 A-allele, rs6520015 C-allele and rs7292407 A-allele (C-A-C-A), suffered a 7.27-fold risk for cardiac pumping function reduction (95% CI: 2.39-22.15, p = .0006) compared with those carrying the wild-type haplotype. CONCLUSIONS:This self-controlled study revealed that PPARA variations significantly increased the risk for cardiac pumping function reductions following acute high-altitude exposure, providing a potential predictive marker before high-altitude exposure and targets in mechanistic studies.

SUBMITTER: Yang J

PROVIDER: S-EPMC6785441 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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PPARA genetic variants increase the risk for cardiac pumping function reductions following acute high-altitude exposure: A self-controlled study.

Yang Jie J Liu Chuan C Jihang Zhang Z Yu Jie J Dai Limeng L Ding Xiaohan X Qiu Youzhu Y Yu Sanjiu S Yang Yuanqi Y Wu Yuzhang Y Huang Lan L

Molecular genetics & genomic medicine 20190812 10

<h4>Background</h4>Left cardiac pumping function determines the compensatory capacity of the cardiovascular system following acute high-altitude exposure. Variations in cardiac output (CO) at high altitude are inconsistent between individuals, and genetic susceptibility may play a crucial role. We sought to identify genetic causes of cardiac pumping function variations and describe the genotype-phenotype correlations.<h4>Methods</h4>A total of 151 young male volunteers were recruited and transfe ...[more]

PMID: 31407515

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Project description:ObjectiveSeveral working groups (eg, miners, flight crews and soldiers) are subjected to chronic intermittent hypoxic exposure. The cardiovascular implications have been studied but not systematically reviewed with focus on possible negative health implications. The aim of the present review was to systematically evaluate the hypothesis that intermittent hypoxic exposure causes cardiovascular stress detrimental to health in workers.DesignSystematic review.Data sourcesElectronic database search of PubMed, Scopus and Web of Science up to April 2020.Eligibility criteriaStudies of workers ≥18 years repeatedly subjected to months to years of irregular intermittent hypoxia, lasting from a few hours (eg, flight crews), one or a few days (eg, soldiers), or several days to weeks (eg, miners working at high altitude), written in English and evaluating the effect of intermittent hypoxia on cardiovascular disease were included. Animal studies, books, book chapters, personal communication and abstracts were excluded. The primary outcome measure was changes in standardised mortality ratio.Data extraction and synthesisTwo independent reviewers extracted data and assessed risk of bias using the Cochrane Collaboration's tool.Results119 articles were identified initially, 31 of which met the inclusion criteria. Of these, 17 were retrospective cohort mortality studies (irregular short-term intermittent hypoxia), and 14 studies were observational (long-term intermittent hypoxia). The population of irregular short-term intermittent hypoxia users (flight crew) showed a lower mortality by cardiovascular disease. Long-term intermittent hypoxia over several years such as in miners or soldiers may produce increased levels of cardiac disorders (12 studies), though this is probably confounded by factors such as obesity and socioeconomic status.ConclusionThis systematic narrative review found that cardiovascular disease mortality in flight crews is lower than average, whereas miners and soldiers exposed to intermittent hypoxia experience increased risks of cardiovascular diseases. The impact of socioeconomic status and lifestyle appears of importance.Prospero registry numberCRD42020171301.

Project description:While much is known about the effects of cocaine use on the cellular structure and function of neurons and synapses within the brain's reward circuitry, relatively little is known about the effects of cocaine on astrocytes. Given the significant role that astrocytes play in modulating neuronal and synaptic function, this lack of knowledge regarding the role of astroglial adaptations in the neuropathology of drug abuse represents an important investigative need. We recently showed that astrocytes within the nucleus accumbens (NAc) core exhibit decreased volume, surface area, and synaptic colocalization following cocaine self-administration and extinction, compared to NAc astrocytes from saline-administering animals (Scofield et al., 2016b). However, it is unknown whether these cocaine-dependent changes in astrocytes are ubiquitous throughout the brain's reward circuitry, or represent specific adaptations within the NAc. It is also not known whether the extinction period is necessary for the retracted phenotype, or whether self-administration alone is sufficient to drive these changes. In the current study, we have extended our assessment of the effects of cocaine self-administration on morphometric properties and synaptic colocalization of astrocyte peripheral processes in the prelimbic region of the medial prefrontal cortex (PL) and basolateral nucleus of the amygdala (BLA), both known to also contribute significantly to motivated behaviors. In addition, in order to pinpoint the temporal dimension of previously observed effects, we also examined astrocytes within the NAc following the last self-administration session. While a reduction of astrocyte size and synaptic colocalization was observed in the NAc core of cocaine-extinguished rats as previously shown, no differences in PL or BLA astrocytes were observed between saline- and cocaine-extinguished rats. Moreover, decreased synaptic colocalization of peripheral processes in the NAc was observed with a post-synaptic marker, instead of a presynaptic marker as used previously. In contrast, no significant changes were found in NAc astrocytes after self-administration alone. These results provide insights into the influence of cocaine use on astrocytes within the brain reward circuitry, and inform both regional heterogeneity as well as temporal dynamics of astrocyte responsiveness to cocaine self-administration.

Dataset Information

PPARA genetic variants increase the risk for cardiac pumping function reductions following acute high-altitude exposure: A self-controlled study.

Publications

PPARA genetic variants increase the risk for cardiac pumping function reductions following acute high-altitude exposure: A self-controlled study.

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