Systolic and diastolic left ventricular function in children with primary hypertension: a systematic review and meta-analysis

Rus, Rina; Pac, Michał; Obrycki, Łukasz; Sağsak, Elif; Ažukaitis, Karolis; Sinha, Manish D.; Jankauskienė, Augustina; Litwin, Mieczysław

doi:10.1097/hjh.0000000000003298

Cited by 8 publications

(5 citation statements)

References 56 publications

(340 reference statements)

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“…Bubenek et al [ 188 ] reported a strong association between NNMT expression, serum MNA levels, and the onset and progression of peripheral arterial occlusive disease. Interestingly, NNMT expression has been found to be positively associated with LDL levels and negatively associated with HDL levels, both of which are factors associated with cardiovascular disease [ 189 , 190 , 191 ].…”

Section: Research Progress On Nnmt In Aging-related Diseasesmentioning

confidence: 99%

Nicotinamide N-Methyltransferase (NNMT): A New Hope for Treating Aging and Age-Related Conditions

Li,

Sun,

Zhu

et al. 2024

Metabolites

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The complex process of aging leads to a gradual deterioration in the function of cells, tissues, and the entire organism, thereby increasing the risk of disease and death. Nicotinamide N-methyltransferase (NNMT) has attracted attention as a potential target for combating aging and its related pathologies. Studies have shown that NNMT activity increases over time, which is closely associated with the onset and progression of age-related diseases. NNMT uses S-adenosylmethionine (SAM) as a methyl donor to facilitate the methylation of nicotinamide (NAM), converting NAM into S-adenosyl-L-homocysteine (SAH) and methylnicotinamide (MNA). This enzymatic action depletes NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and generates SAH, a precursor of homocysteine (Hcy). The reduction in the NAD+ levels and the increase in the Hcy levels are considered important factors in the aging process and age-related diseases. The efficacy of RNA interference (RNAi) therapies and small-molecule inhibitors targeting NNMT demonstrates the potential of NNMT as a therapeutic target. Despite these advances, the exact mechanisms by which NNMT influences aging and age-related diseases remain unclear, and there is a lack of clinical trials involving NNMT inhibitors and RNAi drugs. Therefore, more in-depth research is needed to elucidate the precise functions of NNMT in aging and promote the development of targeted pharmaceutical interventions. This paper aims to explore the specific role of NNMT in aging, and to evaluate its potential as a therapeutic target.

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Section: Research Progress On Nnmt In Aging-related Diseasesmentioning

confidence: 99%

Nicotinamide N-Methyltransferase (NNMT): A New Hope for Treating Aging and Age-Related Conditions

Li,

Sun,

Zhu

et al. 2024

Metabolites

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“…Additionally, Bubenek et al ( Bubenek et al, 2012 ) reported a robust association between NNMT expression, serum MNAM levels, and the onset and progression of peripheral arterial occlusive disease. Notably, NNMT expression has been found to be positively correlated with LDL levels and negatively correlated with HDL levels, both of which are relevant factors in cardiovascular diseases ( Herfindal et al, 2020 ; Kornev et al, 2023 ; Rus et al, 2023 ). As shown in Figure 5 , left ventricular contractile dysfunction and arterial vascular disease are significant contributors to the development of hypertension, suggesting a potential pathway through which NNMT may influence hypertension.…”

Section: Study Progress Of Nnmt In Mets-related Diseasesmentioning

confidence: 99%

Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome

Sun,

Zhu,

et al. 2024

Front. Pharmacol.

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Metabolic syndrome (MetS) represents a constellation of metabolic abnormalities, typified by obesity, hypertension, hyperglycemia, and hyperlipidemia. It stems from intricate dysregulations in metabolic pathways governing energy and substrate metabolism. While comprehending the precise etiological mechanisms of MetS remains challenging, evidence underscores the pivotal roles of aberrations in lipid metabolism and insulin resistance (IR) in its pathogenesis. Notably, nicotinamide N-methyltransferase (NNMT) has recently surfaced as a promising therapeutic target for addressing MetS. Single nucleotide variants in the NNMT gene are significantly correlated with disturbances in energy metabolism, obesity, type 2 diabetes (T2D), hyperlipidemia, and hypertension. Elevated NNMT gene expression is notably observed in the liver and white adipose tissue (WAT) of individuals with diabetic mice, obesity, and rats afflicted with MetS. Knockdown of NNMT elicits heightened energy expenditure in adipose and hepatic tissues, mitigates lipid accumulation, and enhances insulin sensitivity. NNMT catalyzes the methylation of nicotinamide (NAM) using S-adenosyl-methionine (SAM) as the donor methyl group, resulting in the formation of S-adenosyl-l-homocysteine (SAH) and methylnicotinamide (MNAM). This enzymatic process results in the depletion of NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and the generation of SAH, a precursor of homocysteine (Hcy). Consequently, this cascade leads to reduced NAD+ levels and elevated Hcy levels, implicating NNMT in the pathogenesis of MetS. Moreover, experimental studies employing RNA interference (RNAi) strategies and small molecule inhibitors targeting NNMT have underscored its potential as a therapeutic target for preventing or treating MetS-related diseases. Nonetheless, the precise mechanistic underpinnings remain elusive, and as of yet, clinical trials focusing on NNMT have not been documented. Therefore, further investigations are warranted to elucidate the intricate roles of NNMT in MetS and to develop targeted therapeutic interventions.

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“…The significance of early life blood pressure (BP) elevation is well reflected by studies reporting that childhood BP tracks into adulthood and is associated with cardiovascular outcomes, including hypertension-mediated organ damage (HMOD) ( 2 – 4 ). The latter is already apparent in childhood, including changes in left ventricular and vascular structure and function ( 5 – 7 ). Moreover, evidence suggests that pediatric primary hypertension is not a condition characterized by elevated BP alone but represents a phenotype accompanied by changes in body composition, metabolic abnormalities, immune-inflammatory alterations and increased sympathetic activity ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Cognitive performance in children and adolescents with primary hypertension and the role of body mass

Azukaitis,

Puteikis,

Kinciniene

et al. 2024

Front. Pediatr.

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ObjectivePrimary hypertension has been shown to affect cognitive functions in adults but evidence in the pediatric population remain scarce and equivocal. We aimed to compare cognitive functioning between children diagnosed with primary hypertension and normotensive controls, with a focus on the role of different blood pressure (BP) parameters and body mass.MethodsWe conducted a single-center, prospective, cross-sectional study of children and adolescents (6–17 years old) with primary hypertension and age- and sex-matched normotensive controls. All participants underwent office BP, ambulatory BP monitoring (ABPM), and central BP measurements using an oscillometric device. Neurocognitive assessment consisted of evaluation of (i) intelligence quotient (IQ), (ii) categorical and phonemic fluency, (iii) verbal memory (verbal-logical story recall), and (iv) non-verbal computerized cognitive assessment.ResultsThe study included a total of 59 patients with primary hypertension (14 ± 3 years) and 37 normotensive controls (14 ± 3 years). Participants in the primary hypertension group had a significantly higher body mass index z-score (BMIz: 2.1 ± 1.4 vs. 0.7 ± 0.9, p < 0.001), and 85% received antihypertensive therapy. Participants with primary hypertension showed worse performance in the domains of reaction speed, attention and processing speed, visual memory, new learning, and phonemic fluency. After adjusting for BMIz, only the differences in the reaction speed tasks remained significant. None of the BP parameters was associated with cognitive outcomes after adjustment for age, sex, and BMIz. BMIz associated with tasks of visual memory, new learning, spatial planning, and working memory, independent of age and sex.ConclusionChildren and adolescents diagnosed with primary hypertension exhibit worse performance in the cognitive domains of reaction speed, attention, processing speed, visual memory, and new learning. These differences to healthy controls can be partially attributed to accompanying increase of body mass.

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Systolic and diastolic left ventricular function in children with primary hypertension: a systematic review and meta-analysis

Cited by 8 publications

References 56 publications

Nicotinamide N-Methyltransferase (NNMT): A New Hope for Treating Aging and Age-Related Conditions

Nicotinamide N-Methyltransferase (NNMT): A New Hope for Treating Aging and Age-Related Conditions

Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome

Cognitive performance in children and adolescents with primary hypertension and the role of body mass

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