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Tissue Sodium Content and Arterial Hypertension in Obese Adolescents.

ABSTRACT: Early-onset obesity is known to culminate in type 2 diabetes, arterial hypertension and subsequent cardiovascular disease. The role of sodium (Na⁺) homeostasis in this process is incompletely understood, yet correlations between Na⁺ accumulation and hypertension have been observed in adults. We aimed to investigate these associations in adolescents. A cohort of 32 adolescents (13-17 years), comprising 20 obese patients, of whom 11 were hypertensive, as well as 12 age-matched controls, underwent ²³Na-MRI of the left lower leg with a standard clinical 3T scanner. Median triceps surae muscle Na⁺ content in hypertensive obese (11.95 mmol/L [interquartile range 11.62-13.66]) was significantly lower than in normotensive obese (13.63 mmol/L [12.97-17.64]; p = 0.043) or controls (15.37 mmol/L [14.12-16.08]; p = 0.012). No significant differences were found between normotensive obese and controls. Skin Na⁺ content in hypertensive obese (13.33 mmol/L [11.53-14.22] did not differ to normotensive obese (14.12 mmol/L [13.15-15.83]) or controls (11.48 mmol/L [10.48-12.80]), whereas normotensive obese had higher values compared to controls (p = 0.004). Arterial hypertension in obese adolescents is associated with low muscle Na⁺ content. These findings suggest an early dysregulation of Na⁺ homeostasis in cardiometabolic disease. Further research is needed to determine whether this association is causal and how it evolves in the transition to adulthood.

SUBMITTER: Roth S

PROVIDER: S-EPMC6947559 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Tissue Sodium Content and Arterial Hypertension in Obese Adolescents.

Roth Sophie S Markó Lajos L Birukov Anna A Hennemuth Anja A Kühnen Peter P Jones Alexander A Ghorbani Niky N Linz Peter P Müller Dominik N DN Wiegand Susanna S Berger Felix F Kuehne Titus T Kelm Marcus M

Journal of clinical medicine 20191121 12

Early-onset obesity is known to culminate in type 2 diabetes, arterial hypertension and subsequent cardiovascular disease. The role of sodium (Na<sup>+</sup>) homeostasis in this process is incompletely understood, yet correlations between Na<sup>+</sup> accumulation and hypertension have been observed in adults. We aimed to investigate these associations in adolescents. A cohort of 32 adolescents (13-17 years), comprising 20 obese patients, of whom 11 were hypertensive, as well as 12 age-matche ...[more]

PMID: 31766426

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Project description:Pulmonary arterial hypertension (PAH) is a rare disorder associated with high morbidity and mortality despite currently available treatments. We compared the phosphoproteome of lung tissue from subjects with idiopathic PAH (iPAH) obtained at the time of lung transplant with control lung tissue. The mass spectrometry-based analysis found 60,428 phosphopeptide features from which 6622 proteins were identified. Within the subset of identified proteins there were 1234 phosphopeptides with q < 0.05, many of which are involved in immune regulation, angiogenesis, and cell proliferation. Most notably there was a marked relative increase in phosphorylated (S378) IKZF3 (Aiolos), a zinc finger transcription factor that plays a key role in lymphocyte regulation. In vitro phosphorylation assays indicated that GSK3 alpha and/or GSK3 beta could phosphorylate IKZF3 at S378. Western blot analysis demonstrated increased pIKZF3 in iPAH lungs compared to controls. Immunohistochemistry demonstrated phosphorylated IKZF3 in lymphocytes surrounding severely hypertrophied pulmonary arterioles. In situ hybrization showed gene expression in lymphocyte aggregates in PAH samples. A BCL2 reporter assay showed that IKZF3 increased BCL2 promoter activity and demonstrated the potential role of phosphorylation of IKZF3 in the regulation of BCL mediated transcription. Kinase network analysis demonstrated potentially important regulatory roles of casein kinase 2, cyclin-dependent kinase 1 (CDK1), mitogen-associated protein kinases (MAPKs), and protein kinases (PRKs) in iPAH. Bioinformatic analysis demonstrated enrichment of RhoGTPase signaling and the potential importance of cGMP-dependent protein kinase 1 (PRKG). In conclusion, this unbiased phosphoproteomic analysis demonstrated several novel targets regulated by kinase networks in iPAH, and reinforced the potential role of immune regulation in the pathogenesis of iPAH. The identified up- and down-regulated phosphoproteins have potential to serve as biomarkers for PAH and to provide new insights for therapeutic strategies.

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Tissue Sodium Content and Arterial Hypertension in Obese Adolescents.

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Tissue Sodium Content and Arterial Hypertension in Obese Adolescents.

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