Publications by authors named "Ana-Mishel Spiroski"

Gestational hypoxia adversely affects uterine artery function, increasing complications. However, an effective therapy remains unidentified. Here, we show in rodent uterine arteries that hypoxic pregnancy promotes hypertrophic remodelling, increases constrictor reactivity via protein kinase C signalling, and triggers compensatory dilatation via nitric oxide-dependent mechanisms and stimulation of large conductance Ca -activated K -channels.

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Article Synopsis
  • The study explored how human embryonic stem cell-derived endothelial cell products (hESC-ECP) influence tissue remodeling in the heart after an induced heart attack (myocardial infarction) using a mouse model.
  • It found that hESC-ECP therapy effectively reduces the size of the heart infarct and improves heart function measured by echocardiography, compared to control groups.
  • The results suggest that viable hESC-ECP can play a role in the healing process by modulating immune responses and preserving heart tissue, indicating potential new treatments for heart damage.
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Aim: Myocardial infarction remains the leading cause of heart failure. The adult human heart lacks the capacity to undergo endogenous regeneration. New blood vessel growth is integral to regenerative medicine necessitating a comprehensive understanding of the pathways that regulate vascular regeneration.

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Aims: Endothelial cell (EC) dysfunction drives the initiation and pathogenesis of pulmonary arterial hypertension (PAH). We aimed to characterize EC dynamics in PAH at single-cell resolution.

Methods And Results: We carried out single-cell RNA sequencing (scRNA-seq) of lung ECs isolated from an EC lineage-tracing mouse model in Control and SU5416/hypoxia-induced PAH conditions.

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Fetal growth restriction (FGR) is associated with decreased insulin secretory capacity and decreased insulin sensitivity in muscle in adulthood. We investigated whether intra-amniotic IGF-I treatment in late gestation mitigated the adverse effects of FGR on the endocrine pancreas and skeletal muscle at 18 mo of age. Singleton-bearing ewes underwent uterine artery embolization between 103 and 107 days of gestational age, followed by 5 once-weekly intra-amniotic injections of 360-µg IGF-I (FGRI) or saline (FGRS) and were compared with an unmanipulated control group (CON).

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Mitochondria-derived oxidative stress during fetal development increases cardiovascular risk in adult offspring of pregnancies complicated by chronic fetal hypoxia. We investigated the efficacy of the mitochondria-targeted antioxidant MitoQ in preventing cardiovascular dysfunction in adult rat offspring exposed to gestational hypoxia, integrating functional experiments in vivo, with those at the isolated organ and molecular levels. Rats were randomized to normoxic or hypoxic (13%-14% O ) pregnancy ± MitoQ (500 μM day ) in the maternal drinking water.

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Long non-coding RNAs (lncRNAs) have structural and functional roles in development and disease. We have previously shown that the LINC00961/SPAAR (small regulatory polypeptide of amino acid response) locus regulates endothelial cell function, and that both the lncRNA and micropeptide counter-regulate angiogenesis. To assess human cardiac cell SPAAR expression, we mined a publicly available scRNSeq dataset and confirmed LINC00961 locus expression and hypoxic response in a murine endothelial cell line.

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In ST-segment elevation myocardial infarction of both patients and mice, there was a decline in blood eosinophil count, with activated eosinophils recruited to the infarct zone. Eosinophil deficiency resulted in attenuated anti-inflammatory macrophage polarization, enhanced myocardial inflammation, increased scar size, and deterioration of myocardial structure and function. Adverse cardiac remodeling in the setting of eosinophil deficiency was prevented by interleukin-4 therapy.

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Fetal growth restriction (FGR) is associated with compromised growth and metabolic function throughout life. Intrauterine therapy of FGR with intra-amniotic insulin-like growth factor-1 (IGF1) enhances fetal growth and alters perinatal metabolism and growth in a sex-specific manner, but the adult effects are unknown. We investigated the effects of intra-amniotic IGF1 treatment of FGR on adult growth and body composition, adrenergic sensitivity, and glucose-insulin axis regulation.

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Aims: Long non-coding RNAs (lncRNAs) play functional roles in physiology and disease, yet understanding of their contribution to endothelial cell (EC) function is incomplete. We identified lncRNAs regulated during EC differentiation and investigated the role of LINC00961 and its encoded micropeptide, small regulatory polypeptide of amino acid response (SPAAR), in EC function.

Methods And Results: Deep sequencing of human embryonic stem cell differentiation to ECs was combined with Encyclopedia of DNA Elements (ENCODE) RNA-seq data from vascular cells, identifying 278 endothelial enriched genes, including 6 lncRNAs.

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Article Synopsis
  • Chronic fetal hypoxia negatively affects fetal development, leading to long-term health issues in offspring, particularly concerning female reproductive systems.
  • Research using Wistar rats shows that females exposed to chronic hypoxia during gestation had fewer ovarian follicles and shorter telomeres, indicating accelerated ovarian aging and a reduced ovarian reserve.
  • The findings suggest that chronic hypoxia during pregnancy may influence future fertility in subsequent generations, highlighting the vulnerability of ovarian health to gestational complications.
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Article Synopsis
  • Chronic hypoxia during gestation negatively affects long-term reproductive health and development in female offspring, potentially impacting future generations.
  • In a study with female rats, those exposed to chronic hypoxia in utero showed reduced telomere length, mitochondrial DNA production, and increased oxidative stress.
  • These findings suggest that gestational hypoxia accelerates aging in the oviduct and may lead to fertility issues in adulthood.
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The placenta responds to adverse environmental conditions by adapting its capacity for substrate transfer to maintain fetal growth and development. Early-onset hypoxia effects on placental morphology and activation of the unfolded protein response (UPR) were determined using an established rat model in which fetal growth restriction is minimized. We further established whether maternal treatment with a mitochondria-targeted antioxidant (MitoQ) confers protection during hypoxic pregnancy.

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Ischemia-reperfusion (IR) injury occurs when blood supply to an organ is disrupted and then restored, and underlies many disorders, notably myocardial infarction and stroke. While reperfusion of ischemic tissue is essential for survival, it also initiates cell death through generation of mitochondrial reactive oxygen species (ROS). Recent work has revealed a novel pathway underlying ROS production at reperfusion in vivo in which the accumulation of succinate during ischemia and its subsequent rapid oxidation at reperfusion drives ROS production at complex I by reverse electron transport (RET).

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Background: Stroke is the third most common cause of death and a major cause of chronic disability in New Zealand. Linked to risk factors that develop across the life-course, stroke is considered to be largely preventable. This study assessed the awareness of stroke risk, symptoms, detection, and prevention behaviors in an urban New Zealand population.

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Optimal fetal growth is important for a healthy pregnancy outcome and also for lifelong health. Fetal growth is largely regulated by fetal nutrition, and mediated via the maternal and fetal glucose/insulin/insulin-like growth factor axes. Fetal nutrition may reflect maternal nutrition, but abnormalities of placental function can also affect fetal growth, as the placenta plays a key intermediary role in nutritional signalling between mother and fetus.

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