Hop to It: The First Animal Model of Autoimmune Postural Orthostatic Tachycardia Syndrome.
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ABSTRACT:
SUBMITTER: Miller AJ
PROVIDER: S-EPMC6806054 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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Hop to It: The First Animal Model of Autoimmune Postural Orthostatic Tachycardia Syndrome.
Miller Amanda J AJ Doherty Taylor A TA
Journal of the American Heart Association 20190924 19
See Article Li et al. ...[more]
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Project description:The aim of this study was to evaluate the association between postural orthostatic tachycardia syndrome (POTS) and circulating antiganglionic acetylcholine receptor (gAChR) antibodies. We reviewed clinical assessments of Japanese patients with POTS, and determined the presence of gAChR antibodies in serum samples from those patients. Luciferase immunoprecipitation systems detected anti-gAChR ?3 and ?4 antibodies in the sera from POTS (29%). Antecedent infections were frequently reported in patients in POTS patients. Moreover, autoimmune markers and comorbid autoimmune diseases were also frequent in seropositive POTS patients. Anti-gAChR antibodies were detectable in significant number of patients with POTS, and POTS entailed the element of autoimmune basis.
| S-EPMC5899914 | biostudies-literature
Project description:Autoantibodies are implicated in the pathogenesis of cardiovascular diseases and cardiac arrhythmias. In this pilot study, we tested the hypothesis that autoantibodies are present in patients with postural orthostatic tachycardia syndrome (POTS).Seven control subjects (6 F:1 M, average age 36.1 years) and ten patients with the diagnosis of POTS (7 F: 3 M, average age 35.1 years) provided informed consent and 30 mL of venous blood. Human heart membrane proteins were resolved by 2DE and immunoblotted against purified IgGs from controls and patients.Eighteen protein spots immunoreactive specifically against patient IgGs were detected and they were excised from gels, trypsin-digested, and analyzed by nanoLC-electrospray MS/MS. Forty unique proteins were identified and these include proteins that are associated with cardiac hypertrophy (mimecan, myozenin), cardiac remodeling (periostin), cardiomyopathy (desmin, desmoplakin), cell survival (laminin), structural integrity (filamin), chaperone proteins (crystalline, HSP70), mitochondrial enzymes, and channel proteins. Ingenuity Pathway Analysis showed multiple pathways were involved including those that regulate energy metabolism, redox, fibrosis, cardiac hypertrophy, and degeneration.Autoantibodies are present in patients with POTS. These autoantibodies cross-react with a wide range of cardiac proteins and may induce alterations in cardiac function. Autoimmune pathogenetic mechanisms should be further explored in these patients.
| S-EPMC3786406 | biostudies-literature
Project description:Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a cardiovascular autonomic disorder characterized by orthostatic intolerance and high prevalence among young women. The etiology of POTS is uncertain, though autoimmunity and inflammation may play an important role. We aimed to identify novel inflammatory biomarkers associated with POTS. Methods and Results: In the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort, we identified 396 patients (age range, 15-50 years) with either POTS (n = 113) or normal haemodynamic response during passive head-up-tilt test (n = 283). Blood samples were analyzed using antibody-based Proximity Extension Assay technique simultaneously measuring 57 inflammatory protein biomarkers. The discovery algorithm was a sequential two-step process of biomarker signature identification by supervised, multivariate, principal component analysis and verification by univariate ANOVA with Bonferroni correction. POTS patients were younger (26 vs. 31 years; p < 0.001) and there was no significant difference in sex distribution (74% vs. 67% females, p = 0.24). PCA and Bonferroni-adjusted ANOVA identified proconvertase furin as the most robust biomarker signature for POTS. Plasma level of proconvertase furin was lower (6.38 vs. 6.58 of normalized protein expression units (NPX); p < 0.001 in POTS, compared with the reference group. Proconvertase furin met Bonferroni-adjusted significance criteria in both uni- and multivariable regression analyses. Conclusion: Patients with POTS have lower plasma level of proconvertase furin compared with individuals with normal postural hemodynamic response. This finding suggests the presence of a specific autoimmune trait with disruption of immune peripheral tolerance in this hitherto unexplained condition. Further studies are needed for external validation of our results.
| S-EPMC6455076 | biostudies-literature
Project description:Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder leading to debilitating symptoms and the therapeutic alternatives are limited. Proteomics is a large-scale study of proteins that enables a systematic unbiased view on disease and health, allowing stratification on patients based on their protein background. We aimed to explore proteins that may be related with the putative etiology of POTS compared with healthy controls using a highly powerful targeted proteomic mass spectrometry technique. We aimed to explore proteins that may be related with the putative etiology of POTS compared with healthy controls using a highly powerful targeted proteomic mass spectrometry technique.
2022-11-24 | PXD031458 | Pride
Project description:Background: Postural tachycardia syndrome (POTS) is a form of autonomic dysregulation and is characterized by an excessive heart rate (HR) increment upon the upright body position while blood pressure is maintained. Patients experience typical symptoms of orthostatic intolerance such as dizziness, nausea and cognitive impairments. The present study assessed position-dependent attentional and cognitive functioning in POTS patients compared to healthy subjects and tested the response of cognitive performance to acute water intake. Methods: Data was obtained from eight patients with neuropathic POTS and eight healthy subjects of similar age and gender. All participants completed questionnaires that assessed health-related quality of life and depression and underwent four rounds of neuropsychological testing overall, each before and after the intake of 500 ml still mineral water and both in the supine and in the upright posture. Results: Postural tachycardia syndrome patients showed deficits in working memory (WM) exclusively in the upright position compared to healthy subjects, but no position-dependent impairments in alertness or divided attention. Rapid water ingestion had a beneficial effect on WM in the upright posture, lead to a decrease in HR increment and to an improvement of subjective symptom experience. Conclusion: The results provide support for the occurrence of purely orthostatic cognitive deficits in POTS, especially when increased executive control and cognitive resources are required and document a favorable effect of water intake on cognitive performance. These findings have important implications for the management of cognitive symptoms in POTS as high water intake is an easy and accessible strategy.
| S-EPMC6465605 | biostudies-literature
Project description:AimsPostural orthostatic tachycardia syndrome (POTS) is a disorder of unknown aetiology characterized by orthostatic intolerance and tachycardia with diverse other symptoms, including neurocognitive deficits. Cerebral oximetry non-invasively measures cerebral tissue saturation (SctO2) and has been shown to be informative in syncope evaluation. We aimed to assess SctO2 in POTS patients and those with normal response to orthostatic provocation, relative to haemodynamic parameters and symptoms.Methods and resultsThirty-four patients with POTS (29.1 ± 9.5 years; 26 females) and 34 age-/sex-matched controls with normal head-up tilt tests (HUTs) were included. SctO2 at rest and during HUT were compared between POTS and controls. The relation between SctO2, systolic blood pressure (SBP), and heart rate (HR) during HUT was linearly assessed. SctO2 values were related to dizziness or syncope during HUT. The minimum SctO2-value during HUT was lower (65.4 ± 5.6 vs. 68.2 ± 4.2%, P = 0.023) and changes in SctO2 from supine to minimum HUT value were more pronounced in POTS patients (-5.7 ± 2.9% vs. -4.3 ± 2.1%, P = 0.028). Decrease in SBP from supine to minimum HUT value (P = 0.004) and increase in HR from supine to HUT value at 3 min (P = 0.022) correlated with more pronounced SctO2 decrease in POTS but not controls. SctO2 did not predict syncope or dizziness during HUT.ConclusionPostural orthostatic tachycardia syndrome patients have lower cerebral tissue saturation during orthostatic provocation compared with those subjects having normal haemodynamic response to tilt. Orthostatic decrease in cerebral saturation only weakly correlates with HR increase and does not predict vasovagal reflex in POTS. Other hitherto unknown factors may affect cerebral tissue saturation in POTS.
| S-EPMC6877984 | biostudies-literature
Project description:BACKGROUND:Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular (CV) autonomic disorder of unknown etiology characterized by an excessive heart rate increase on standing and orthostatic intolerance. In this study we sought to identify novel CV biomarkers potentially implicated in POTS pathophysiology. METHODS:We conducted a nested case-control study within the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort including 396 patients (age range, 15-50?years) with either POTS (n?=?113) or normal hemodynamic response during passive head-up-tilt test (n?=?283). We used a targeted approach to explore changes in cardiovascular proteomics associated with POTS through a sequential two-stage process including supervised principal component analysis and univariate ANOVA with Bonferroni correction. RESULTS:POTS patients were younger (26 vs. 31?years; p?<?0.001) and had lower BMI than controls. The discovery algorithm identified growth hormone (GH) and myoglobin (MB) as the most specific biomarker fingerprint for POTS. Plasma level of GH was higher (9.37 vs 8.37 of normalised protein expression units (NPX); p?=?0.002), whereas MB was lower (4.86 vs 5.14 NPX; p?=?0.002) in POTS compared with controls. In multivariate regression analysis, adjusted for age and BMI, and stratified by sex, lower MB level in men and higher GH level in women remained independently associated with POTS. CONCLUSIONS:Cardiovascular proteomics analysis revealed sex-specific biomarker signature in POTS featured by higher plasma level of GH in women and lower plasma level of MB in men. These findings point to sex-specific immune-neuroendocrine dysregulation and deconditioning as potentially key pathophysiological traits underlying POTS.
| S-EPMC7178975 | biostudies-literature
Project description:BackgroundPostural orthostatic tachycardia syndrome (POTS) is a debilitating form of chronic orthostatic intolerance that primarily affects women and causes substantial impairment in quality of life and function. Yet, there is minimal literature describing the employment and economic consequences of POTS. We explored these aspects of the POTS patient experience through a self-reported study designed using community-based participatory research principles.Methods and resultsA comprehensive questionnaire, including employment and economic consequences, was developed in partnership with Dysautonomia International, a patient advocacy organization. The POTS community engaged in all stages of the research design and analysis. Participants were recruited through Dysautonomia International's website and social media channels. The analysis included 5,556 adult (age ≥18 years) participants with a physician-confirmed diagnosis of POTS. The majority of participants were female (95%). Forty-eight per cent of participants reported employment during the three months prior to the survey, and of these participants, 66.8% would work greater hours if not for illness limitations. Over two-thirds (70.5%) of participants have lost income due to POTS symptoms, with 36.0% of the total cohort losing more than $10,000 USD in the 12 months prior to the survey. Almost all (95%) participants reported POTS-related out-of-pocket medical expenses since diagnosis, with 51.1% of participants spending $10,000 USD or more.ConclusionsThis is the largest study reporting the employment and economic challenges experienced by individuals with POTS. Exposure of these challenges emphasizes the need for earlier diagnosis and improved therapeutic strategies to reduce the negative individual and societal consequences of this disorder.
| S-EPMC9156448 | biostudies-literature
Project description:We have found recently that exercise training is effective in the treatment of the postural orthostatic tachycardia syndrome (POTS). Whether this nondrug treatment is superior to "standard" drug therapies, such as ?-blockade, is unknown. We tested the hypothesis that exercise training but not ?-blockade treatment improves symptoms, hemodynamics, and renal-adrenal responses in POTS patients. Nineteen patients (18 women and 1 man) completed a double-blind drug trial (propranolol or placebo) for 4 weeks, followed by 3 months of exercise training. Fifteen age-matched healthy individuals (14 women and 1 man) served as controls. A 2-hour standing test was performed before and after drug treatment and training. Hemodynamics, catecholamines, plasma renin activity, and aldosterone were measured supine and during 2-hour standing. We found that both propranolol and training significantly lowered standing heart rate. Standing cardiac output was lowered after propranolol treatment (P=0.01) but was minimally changed after training. The aldosterone:renin ratio during 2-hour standing remained unchanged after propranolol treatment (4.1±1.7 [SD] before versus 3.9±2.0 after; P=0.46) but modestly increased after training (5.2±2.9 versus 6.5±3.0; P=0.05). Plasma catecholamines were not affected by propranolol or training. Patient quality of life, assessed using the 36-item Short-Form Health Survey, was improved after training (physical functioning score 33±10 before versus 50±9 after; social functioning score 37±9 versus 48±6; both P<0.01) but not after propranolol treatment (34±10 versus 36±11, P=0.63; 39±7 versus 39±5, P=0.73). These results suggest that, for patients with POTS, exercise training is superior to propranolol at restoring upright hemodynamics, normalizing renal-adrenal responsiveness, and improving quality of life.
| S-EPMC3142863 | biostudies-other
Project description:Background Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive heart rate increase on standing and orthostatic intolerance. Previous data indicate autoimmune involvement. We studied serum activity against G protein-coupled receptors in relation to symptoms in patients with POTS and controls using a commercial cell-based assay. Methods and Results Forty-eight patients with POTS (aged 28.6±10.5 years; 44 women) and 25 healthy individuals (aged 30.7±8.6 years; 21 women) were included. The 10-item Orthostatic Hypotension Questionnaire (OHQ) was completed by 33 patients with POTS and all controls. Human embryonic kidney 293 cells overexpressing one G protein-coupled receptor: adrenergic α1 receptor, adrenergic β2 receptor, cholinergic muscarinic type 2 receptor, and opioid receptor-like 1 were treated with sera from all patients. Receptor response was analyzed using a β-arrestin-linked transcription factor driving transgenic β-lactamase transcription by fluorescence resonance energy transfer method. Receiver operating characteristic curves were constructed. G protein-coupled receptor activation was related to OHQ indices in linear regression models. Sera from patients with POTS activated all 4 receptors to a higher degree compared with controls (P<0.01 for all). The area under the curve was 0.88 (0.80-0.97, P<0.001) combining all 4 receptors. Adrenergic α1 receptor activation associated with OHQ composite score (β=0.77 OHQ points per SD of activity, P=0.009) and with reduced tolerability for prolonged standing (P=0.037) and walking for short (P=0.042) or long (P=0.001) periods. All 4 receptors were associated with vision problems (P<0.05 for all). Conclusions Our results indicate the presence of circulating proteins activating adrenergic, muscarinic, and nociceptin receptors in patients with POTS. Serum-mediated activation of these receptors has high predictive value for POTS. Activation of adrenergic α1 receptor is associated with orthostatic symptoms severity in patients with POTS.
| S-EPMC7792263 | biostudies-literature