Dataset Information

Novel Targeted Proteomic Profiling of Potential Biomarkers in Postural Orthostatic Tachycardia Syndrome (POTS)

ABSTRACT: 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.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Postural Orthostatic Tachycardia Syndrome

SUBMITTER: Charlotte Welinder

LAB HEAD: Madeleine Johansson

PROVIDER: PXD031458 | Pride | 2022-11-24

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	2021-06-28_HY_POTS_Plasma_01_EV1109_60SPD_500ng_diaPASEF_S1-A1_1_1438.mzML	Mzml
	2021-06-28_HY_POTS_Plasma_02_EV1109_60SPD_500ng_diaPASEF_S1-A2_1_1439.mzML	Mzml
	2021-06-28_HY_POTS_Plasma_03_EV1109_60SPD_500ng_diaPASEF_S1-A3_1_1440.mzML	Mzml
	2021-06-28_HY_POTS_Plasma_05_EV1109_60SPD_500ng_diaPASEF_S1-A5_1_1442.mzML	Mzml
	2021-06-28_HY_POTS_Plasma_06_EV1109_60SPD_500ng_diaPASEF_S1-A6_1_1443.mzML	Mzml

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Publications

Plasma proteomic profiling in postural orthostatic tachycardia syndrome (POTS) reveals new disease pathways.

Johansson Madeleine M Yan Hong H Welinder Charlotte C Végvári Ákos Á Hamrefors Viktor V Bäck Magnus M Sutton Richard R Fedorowski Artur A

Scientific reports 20221121 1

Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder characterized by excessive heart rate increase on standing, leading to debilitating symptoms with limited therapeutic possibilities. Proteomics is a large-scale study of proteins that enables a systematic unbiased view on disease and health, allowing stratification of patients based on their protein background. The aim of the present study was to determine plasma protein biomarkers of POTS and to reveal prote ...[more]

PMID: 36414707

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Project description:Background Muscle ageing contributes to both loss of functional autonomy and increased morbidity. Muscle atrophy accelerates after 50 years of age, but the mechanisms involved are complex and likely result from the alteration of a variety of interrelated functions. In order to better understand the molecular mechanisms underlying muscle chronological ageing in human, we have undertaken a top-down differential proteomic approach to identify novel biomarkers after the fifth decade of age. Results Muscle samples were compared between adult (56 years) and old (78 years) post-menopausal women. In addition to total muscle extracts, low-ionic strength extracts were investigated to remove high abundance myofibrillar proteins and improve the detection of low abundance proteins. Two-dimensional gel electrophoreses with overlapping IPGs were used to improve the separation of muscle proteins. Overall, 1919 protein spots were matched between all individuals, 95 were differentially expressed and identified by mass spectrometry, and they corresponded to 67 different proteins. Our results suggested important modifications in cytosolic, mitochondrial and lipid energy metabolism, which may relate to dysfunctions in old muscle force generation. A fraction of the differentially expressed proteins were linked to the sarcomere and cytoskeleton (myosin light-chains, troponin T, ankyrin repeat domain-containing protein-2, vinculin, four and a half LIM domain protein-3), which may account for alterations in contractile properties. In line with muscle contraction, we also identified proteins related to calcium signal transduction (calsequestrin-1, sarcalumenin, myozenin-1, annexins). Muscle ageing was further characterized by the differential regulation of several proteins implicated in cytoprotection (catalase, peroxiredoxins), ion homeostasis (carbonic anhydrases, selenium-binding protein 1) and detoxification (aldo-keto reductases, aldehyde dehydrogenases). Notably, many of the differentially expressed proteins were central for proteostasis, including heat shock proteins and proteins involved in proteolysis (valosin-containing protein, proteasome subunit beta type-4, mitochondrial elongation factor-Tu). Conclusions This study describes the most extensive proteomic analysis of muscle ageing in humans, and identified 34 new potential biomarkers. None of them were previously recognized as differentially expressed in old muscles, and each may represent a novel starting point to elucidate the mechanisms of muscle chronological ageing in humans.