Epigenomic changes associated with impaired norepinephrine transporter function in postural tachycardia syndrome

Khan, Abdul Waheed; Corcoran, Susan J.; Esler, Murray; El‐Osta, Assam

doi:10.1016/j.neubiorev.2016.06.015

Cited by 12 publications

(10 citation statements)

References 104 publications

(15 reference statements)

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“…An increase in plasma norepinephrine in the standing position is the main biochemical change that occurs in hyperadrenergic POTS patients (38)(39)(40). Zhang et al (38) reported that the plasma norepinephrine level in the upright position was positively associated with the severity of symptoms and the HR increase in the HUTT in pediatric POTS patients, and they speculated that the orthostatic norepinephrine increase might be due to the decreased vasoconstriction mediated by the baroreflex upon standing.…”

Section: Abnormal Autonomic Reflexes and A "Hyperadrenergic" Statusmentioning

confidence: 99%

“…Zhang et al (38) reported that the plasma norepinephrine level in the upright position was positively associated with the severity of symptoms and the HR increase in the HUTT in pediatric POTS patients, and they speculated that the orthostatic norepinephrine increase might be due to the decreased vasoconstriction mediated by the baroreflex upon standing. Elevated plasma norepinephrine in pediatric patients with POTS suggests an impaired function of the norepinephrine transporter (NET) (39). Studies have shown that inherited or acquired mutations of NET encoded by the solute carrier family 6 neurotransmitter transporter noradrenalin member 2 (SLC6A2) gene impair the removal of norepinephrine in the synaptic cleft and reduce NET-dependent norepinephrine reabsorption (39,40).…”

Section: Abnormal Autonomic Reflexes and A "Hyperadrenergic" Statusmentioning

confidence: 99%

“…Elevated plasma norepinephrine in pediatric patients with POTS suggests an impaired function of the norepinephrine transporter (NET) (39). Studies have shown that inherited or acquired mutations of NET encoded by the solute carrier family 6 neurotransmitter transporter noradrenalin member 2 (SLC6A2) gene impair the removal of norepinephrine in the synaptic cleft and reduce NET-dependent norepinephrine reabsorption (39,40). The above data suggest that changes in the SLC6A2 gene or NET protein expression eventually lead to increased adrenaline status in "hyperadrenergic" POTS patients.…”

Section: Abnormal Autonomic Reflexes and A "Hyperadrenergic" Statusmentioning

confidence: 99%

“…Owing to frequent incapacitating symptoms of POTS that are closely related to an upright posture especially in stifling conditions (2), patients should avoid long periods of standing, sudden head-up postural changes, and high environmental temperatures (5). For POTS patients with a "hyperadrenergic" background, infection, sympathetic activation, and a lack of sleep might aggravate symptoms (4,38,39). Thus, patients are prevented from taking drugs such as NET inhibitors or 5-hydroxytryptamine norepinephrine reuptake inhibitors (5).…”

Section: Non-pharmacological Interventionsmentioning

confidence: 99%

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Postural Tachycardia Syndrome in Children and Adolescents: Pathophysiology and Clinical Management

Chen

Jin

et al. 2020

Front. Pediatr.

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Postural tachycardia syndrome (POTS), characterized by chronic (≥6 months) orthostatic intolerance symptoms with a sustained and excessive heart rate increase while standing without postural hypotension, is common in children and adolescents. Despite the unclear pathogenesis of POTS, the present opinion is that POTS is a heterogeneous and multifactorial disorder that includes altered central blood volume, abnormal autonomic reflexes, "hyperadrenergic" status, damaged skeletal muscle pump activity, abnormal local vascular tension and vasoactive factor release, mast cell activation, iron insufficiency, and autoimmune dysfunction. A number of pediatric POTS patients are affected by more than one of these pathophysiological mechanisms. Therefore, individualized treatment strategies are initiated in the management of POTS, including basal non-pharmacological approaches (e.g., health education, the avoidance of triggers, exercise, or supplementation with water and salt) and special pharmacological therapies (e.g., oral rehydration salts, midodrine hydrochloride, and metoprolol). As such, the recent progress in the pathogenesis, management strategies, and therapeutic response predictors of pediatric POTS are reviewed here.

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Section: Abnormal Autonomic Reflexes and A "Hyperadrenergic" Statusmentioning

confidence: 99%

Section: Abnormal Autonomic Reflexes and A "Hyperadrenergic" Statusmentioning

confidence: 99%

Section: Abnormal Autonomic Reflexes and A "Hyperadrenergic" Statusmentioning

confidence: 99%

Section: Non-pharmacological Interventionsmentioning

confidence: 99%

See 2 more Smart Citations

Postural Tachycardia Syndrome in Children and Adolescents: Pathophysiology and Clinical Management

Chen

Jin

et al. 2020

Front. Pediatr.

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show abstract

“…They focus their attention on the gene that encodes for the norephrine transporter (SLC6A2) and highlight the potential therapeutic application of strategies that target the epigenetic mechanisms implicated in the regulation of SLC6A2 expression in POTS (Khan et al, 2017). …”

mentioning

confidence: 99%