Gender‐dependent hypoxic tolerance mediated via gender‐specific mechanisms

Arnim, Christine A. F. Von; Etrich, S M; Timmler, Melanie; Riepe, Matthias W.

doi:10.1002/jnr.10195

Cited by 23 publications

(10 citation statements)

References 23 publications

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“…Variants in adenosine receptor genes including ADORA3 and ADORA1 may predict cardiac response to ischemia or injury 32. Upregulation of adenosine A3 receptors mRNA upon preconditioning is sex specific and depends on a woman's menstrual cycle 33. In this study, the gene region of A1 receptors was alike in both women and men.…”

Section: Discussionmentioning

confidence: 64%

Sex‐Specific Genetic Variants are Associated With Coronary Endothelial Dysfunction

Yoshino

Cilluffo

Prasad

et al. 2016

JAHA

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BackgroundEndothelial dysfunction is an early stage of atherosclerosis. Single‐nucleotide polymorphisms (SNPs) have been associated with vascular dysfunction, cardiac events, and coronary artery remodeling. We aimed to detect SNPs associated with endothelial dysfunction and determine whether these associations are sex specific.Methods and ResultsSix hundred forty‐three subjects without significant obstructive coronary artery disease underwent invasive coronary endothelial function assessment. We collected data from 1536 SNPs that had previously been associated with vasoreactivity, angiogenesis, inflammation, artery calcification, atherosclerotic risk factors, insulin resistance, hormone levels, blood coagulability, or with coronary heart disease. Coronary vascular reactivity was assessed by the percent change in coronary artery diameter ≤ −20% after an intracoronary bolus injection of acetylcholine on invasive coronary physiology study. SNPs significantly associated with coronary epicardial endothelial dysfunction were ADORA1,KCNQ1, and DNAJC4 in the whole cohort, LPA, MYBPH, ADORA3, and PON1 in women and KIF6 and NFKB1 in men (P<0.01).ConclusionsWe have identified several significant SNPs that are associated with an increased risk of coronary endothelial dysfunction. These associations appear to be sex specific and may explain gender‐related differences in development of atherosclerosis.

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Section: Discussionmentioning

confidence: 64%

Sex‐Specific Genetic Variants are Associated With Coronary Endothelial Dysfunction

Yoshino

Cilluffo

Prasad

et al. 2016

JAHA

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“…Sex-specific isoflurane preconditioning in ischemic brain H Kitano et al tolerance of hippocampal slices from mice chemically preconditioned with 3-nitro-propionate concluded that hypoxic tolerance and preconditioning are gender-dependent and modulated during the estrous cycle by gender-specific mechanisms (Kasischke et al, 1999;Von Arnim et al, 2002). These observations challenge the assumption that the general response to preconditioning is similar in brains of either sex.…”

Section: Discussionmentioning

confidence: 99%

Gender-Specific Response to Isoflurane Preconditioning in Focal Cerebral Ischemia

Kitano

Young

Cheng

et al. 2007

J Cereb Blood Flow Metab

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Inhalation anesthetics are effective chemical preconditioning agents in experimental cerebral ischemia. However, previous work has been performed exclusively in male animals. We determined if there is a gender difference in ischemic outcome after isoflurane preconditioning (IsoPC), and if this sex-specific response is linked to differences in Akt phosphorylation or expression of neuronal inducible cell-death putative kinase (NIPK), a negative modulator of Akt activation. Young and middle-aged male and female mice were preconditioned for 4 h with air (sham PC) or 1.0% IsoPC and recovered for 24 h. Cortices were subdissected from preconditioned young male and female mice for measurement of Akt phosphorylation (Western blot) and NIPK mRNA (quantitative polymerase chain reaction). Additional cohorts underwent 2 h of reversible middle cerebral artery occlusion. Lastly, male and female Akt1+/+ and Akt1−/– mice were studied to determine if gender differences in ischemic outcome after IsoPC is Akt1-dependent. Infarction volume was determined at 22 h reperfusion (2,3,5-triphenyltetrazolium chloride). As expected, IsoPC decreased ischemic damage as compared with sham PC in young and middle-aged male mice. In contrast, IsoPC markedly increased infarction in young female mice and had no effect in middle-aged female mice. Cortical phospho-Akt was increased by IsoPC versus sham PC only in male mice. No increase was observed in IsoPC female mice. NIPK mRNA was higher in female mice than in male mice regardless of preconditioning status. Male IsoPC neuroprotection was lost in Akt1-deficient male mice. We conclude that IsoPC is beneficial only in ischemic male brain and that sex differences in IsoPC are mediated through Akt activation and basal NIPK expression.

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“…Our study did not address this controversy but used fundamental paradigms to test estradiol signaling and IsoPC mechanisms, as little work has been done evaluating the role of ERs in anesthetic or other forms of preconditioning in the ischemic female brain. For example, in a model of hypoxic tolerance using mice preconditioned with 3-nitro-propionate, Von Arnim et al (2002) have observed that ER α mRNA levels were found to be similar in males and females and were unaltered by 3-nitropropionate preconditioning. Interestingly, increased protein levels of ER α but not ER β in the cortex were observed 24 h after hypoxic preconditioning in neonatal rats (Cimarosti et al , 2005).…”

Section: Discussionmentioning

confidence: 99%

Estradiol Attenuates Neuroprotective Benefits of Isoflurane Preconditioning in Ischemic Mouse Brain

Wang

Kitano

Hurn

et al. 2008

J Cereb Blood Flow Metab

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Isoflurane preconditioning (IsoPC) neuroprotection in experimental stroke is male-specific. We determined whether estradiol alters ischemic outcomes in IsoPC brain and examined the role of estrogen receptors (ERs). Seven to 10 days before preconditioning, ovariectomized (OVX) mice were implanted with estradiol, vehicle, or ER subtype agonists. OVX ± estradiol, OVX ± vehicle, OVX ± ER agonists, and ER subtype wild-type (WT) and knockout (KO) mice were preconditioned for 4 h with sham anesthetic preconditioning (sham PC) or 1% IsoPC and recovered for 24 h. Mice then underwent 2 h of middle cerebral artery occlusion followed by 22 h of reperfusion. Infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride staining, with comparisons between IsoPC and corresponding sham PC for each treatment group. Decreased infarct injury was seen in IsoPC OVX ± vehicle, whereas estradiol in IsoPC OVX mice enhanced ischemic damage. In ER studies, increased infarct volumes were seen in IsoPC ERWT mice regardless of ER subtype. IsoPC in ERαKO mice had no effect on infarction volume but reduced only cortical ischemic damage in ERβKO mice. In OVX + ERα agonist, IsoPC had no effect on infarction volume. In OVX + ERβ agonist, IsoPC increased cortical infarct volume. Estradiol depresses the brain’s protective response to IsoPC and may exacerbate cortical ischemic injury mainly through an ERβ-dependent mechanism.

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Gender‐dependent hypoxic tolerance mediated via gender‐specific mechanisms

Cited by 23 publications

References 23 publications

Sex‐Specific Genetic Variants are Associated With Coronary Endothelial Dysfunction

Sex‐Specific Genetic Variants are Associated With Coronary Endothelial Dysfunction

Gender-Specific Response to Isoflurane Preconditioning in Focal Cerebral Ischemia

Estradiol Attenuates Neuroprotective Benefits of Isoflurane Preconditioning in Ischemic Mouse Brain

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