Metabolomic Signature of Early Vascular Aging (EVA) in Hypertension.
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ABSTRACT:
SUBMITTER: Polonis K
PROVIDER: S-EPMC7019377 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Metabolomic Signature of Early Vascular Aging (EVA) in Hypertension.
Polonis Katarzyna K Wawrzyniak Renata R Daghir-Wojtkowiak Emilia E Szyndler Anna A Chrostowska Marzena M Melander Olle O Hoffmann Michał M Kordalewska Marta M Raczak-Gutknecht Joanna J Bartosińska Ewa E Kaliszan Roman R Narkiewicz Krzysztof K Markuszewski Michał J MJ
Frontiers in molecular biosciences 20200207
Arterial stiffening is a hallmark of early vascular aging (EVA) syndrome and an independent predictor of cardiovascular morbidity and mortality. In this case-control study we sought to identify plasma metabolites associated with EVA syndrome in the setting of hypertension. An untargeted metabolomic approach was used to identify plasma metabolites in an age-, BMI-, and sex-matched groups of EVA (<i>n</i> = 79) and non-EVA (<i>n</i> = 73) individuals with hypertension. After raw data processing an ...[more]
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Project description:<p>Arterial stiffening is a hallmark of early vascular aging (EVA) syndrome and an independent predictor of cardiovascular morbidity and mortality. In this case-control study we sought to identify plasma metabolites associated with EVA syndrome in the setting of hypertension. An untargeted metabolomic approach was used to identify plasma metabolites in an age-, BMI- and sex-matched groups of EVA (n = 79) and non-EVA (n = 73) individuals with hypertension. After raw data processing and filtration, 497 putative compounds were characterized, out of which 4 were identified as lysophosphaditylcholines (LPCs) [LPC (18:2), LPC (16:0), LPC (18:0) and LPC (18:1)]. A main finding of this study shows that identified LPCs were independently associated with EVA status. Although LPCs have been shown previously to be positively associated with inflammation and atherosclerosis, we observed that hypertensive individuals characterized by 4 down-regulated LPCs had 3.8 times higher risk of EVA compared to those with higher LPC levels (OR = 3.8, 95% CI 1.7 – 8.5, P < .001). Our results provide new insights into a metabolomic phenotype of vascular aging and warrants further investigation of negative association of LPCs with EVA status. This study suggests that LPCs are potential candidates to be considered for further evaluation and validation as predictors of EVA in patients with hypertension </p>
2020-01-14 | MTBLS1359 | MetaboLights
Project description:BackgroundPreeclampsia (PE) is associated with increased cardiovascular risk. Recent data have shown worse left ventricular remodeling and diastolic function in women with PE and persistent hypertension (HTN). We performed a comprehensive arterial hemodynamic assessment to evaluate the contribution of persistent HTN on arterial health after PE.MethodsWe recruited 40 women with PE history and 40 age-matched controls (6 months to 6 years postpartum). We evaluated arterial hemodynamics with validated techniques combining applanation tonometry and transthoracic echocardiography, comparing three groups: previous PE with persistent HTN (PE-HTN), previous PE with normalized blood pressure (PE-noHTN) and controls, using multivariable linear regression adjusted for age, body surface area, heart rate, diabetes, smoking history, creatinine, and gravidity.ResultsEight (20%) of the post-PE women had persistent HTN. Mean age was 35.8 ± 3.9 years, median number of pregnancies was 2 (range 1-7), and time since last pregnancy 2.1 (range 0.5-5.7) years (not different between groups, P > 0.05). Compared to controls and to PE-noHTN, PE-HTN had higher aortic stiffness, wave reflections, pulsatile, and steady arterial load (P < 0.05 for each). Among PE-noHTN, aortic stiffness, wave reflections and steady arterial load were worse than controls (P < 0.05 for each), with smaller effect sizes.ConclusionsThis is the most comprehensive assessment of arterial hemodynamics and first to demonstrate the contribution of persistent HTN on worse arterial health following PE. Since measures of arterial health are associated with cardiovascular events in the population, the combination of previous PE and chronic HTN may represent a higher risk subgroup who could benefit from targeted prevention strategies.
| S-EPMC10724522 | biostudies-literature
Project description:Background Early vascular aging (EVA) is associated with higher risk of adverse cardiovascular events and can be estimated noninvasively by assessing arterial hemodynamics. Women with a history of preeclampsia have increased risk of cardiovascular disease, but underlying mechanisms are incompletely understood. We hypothesized that women with a history of preeclampsia display persistent arterial abnormalities and EVA in the postpartum period. Methods and Results We performed a comprehensive, noninvasive arterial hemodynamic evaluation in women with a history of preeclampsia (n=40) and age-matched controls with previous normotensive pregnancies (n=40). We used validated methods integrating applanation tonometry with transthoracic echocardiography to obtain measures of aortic stiffness, steady and pulsatile arterial load, central blood pressure, and arterial wave reflections. Presence of EVA was defined as aortic stiffness higher than that predicted from reference values based on the participant's age and blood pressure. The association of preeclampsia with arterial hemodynamic variables was assessed with multivariable linear regression, and the association of severe preeclampsia with EVA was assessed with multivariable logistic regression, adjusted for confounders. We found that women with a history of preeclampsia had greater aortic stiffness, steady arterial load, central blood pressure, and arterial wave reflections when compared with controls. We observed a dose-response relationship, with the greatest abnormalities observed in subgroups with severe, preterm, or recurrent preeclampsia. Women with severe preeclampsia had 9.23 times greater odds of having EVA as compared with controls (95% CI, 1.67-51.06, P=0.011) and 7.87 greater odds of EVA as compared with women with nonsevere preeclampsia (95% CI, 1.29-47.77, P=0.025). Conclusions Our study comprehensively characterizes arterial hemodynamic abnormalities after preeclampsia and suggests that specific subgroups of women with a history of preeclampsia exhibit greater alterations in arterial hemodynamics related to arterial health. Our findings have important implications for understanding potential links between preeclampsia and cardiovascular events, and suggest women with severe, preterm, or recurrent preeclampsia as subgroups who may deserve intensification of efforts for prevention and early detection of cardiovascular disease.
| S-EPMC10227279 | biostudies-literature
Project description:BackgroundIn contrast to severe gestational hypertension, it is questioned whether antihypertensive medication for mild to moderate gestational hypertension prevents adverse maternal and offspring outcomes. Hypertensive drugs halve the risk of severe hypertension, but do not seem to prevent progression to preeclampsia or reduce the risk of complications in offspring. In fact, beta-blockers, a first line therapy option, are suspected to impair foetal growth. Disappointing effects of antihypertensive medication can be anticipated when the pharmacological mode of action does not match the underlying haemodynamic imbalance. Hypertension may result from 1) high cardiac output, low vascular resistance state, in which beta blockade is expected to be most effective, or 2) low cardiac output, high vascular resistance state where dihydropyridine calcium channel blockers or central-acting alpha agonists might be the best corrective medication. In the latter, beta-blockade might be maternally ineffective and even contribute to impaired foetal growth by keeping cardiac output low. We propose a randomized controlled trial to determine whether correcting the haemodynamic imbalance in women with mild to moderate hypertension reduces the development of severe hypertension and/or preeclampsia more than non-pharmacological treatment does, without alleged negative effects on foetal growth.MethodsWomen diagnosed with mild to moderate hypertension without proteinuria or signs of other organ damage before 37 weeks of pregnancy are invited to participate in this randomized controlled trial. Women randomized to the intervention group will be prescribed tailored antihypertensive medication, using a simple diagnostic and treatment algorithm based on the mean arterial pressure/heart rate ratio, which serves as an easy-to-determine proxy for maternal circulatory state. Women randomized to the control group will receive non-pharmacological standard care according to national and international guidelines. In total, 208 women will be randomized in a 1:1 ratio. The primary outcome is progression to severe hypertension and preeclampsia and the secondary outcomes are adverse maternal and neonatal outcomes.DiscussionThis trial will provide evidence of whether tailoring treatment of mild to moderate gestational hypertension to the individual haemodynamic profile prevents maternal disease progression.Trial registrationNCT02531490 , registered on 24 August 2015.
| S-EPMC7733247 | biostudies-literature
Project description:The objective of this study is to analyze the influence of adherence to the Mediterranean diet (MDA) and its components on early vascular aging (EVA) in a Spanish population sample free of cardiovascular disease and to analyze the differences by sex. METHODS:We recruited 501 individuals aged 35-75 without cardiovascular disease by random sampling (55.90 ± 14.24 years, 49.70% men). EVA was defined in two steps: Step 1: subjects with vascular damage in carotid arteries or peripheral artery disease were classified as EVA. Step 2: subjects at the percentile of the combined Vascular Aging Index (VAI) were classified; ? p90 was considered EVA and < p90 was considered normal vascular aging (NVA), estimated using the following formula (VAI = (log (1.09) × 10 cIMT + log (1.14) cfPWV) × 39.1 + 4.76 by age and sex. Carotid-femoral pulse wave velocity (cfPWV) was measured by SphigmoCor System® and carotid intima-media thickness by Sonosite Micromax® ultrasound and classified thus: values ? Percentile 90 were considered EVA and those < Percentile 90 as NVA, with population percentiles analyzed. The principal result variable was assessed using the 14-item MEDAS questionnaire, developed and validated by the PREDIMED group, comprising 12 questions about the frequency of food consumption and two questions regarding the Spanish population's typical eating habits. RESULTS:MDA was observed by 25% (17% men and 34% women). EVA was present in 17% (29% men and 4% women). The adjusted logistic regression models showed that an increase in MDA decreases the probability of EVA in the global analysis (OR = 0.36; 95% CI: 0.16-0.82). In the analysis by sex, this association was only seen in men (OR = 0.33; 95% CI: 0.12-0.86), but not in women (OR = 0.31; 95% CI: 0.04-2.50). CONCLUSION:The results of this study suggest that a greater adherence to the Mediterranean diet decreases the probability of presenting EVA. In the analysis by sex, this association applies only to men.
| S-EPMC7231158 | biostudies-literature
Project description:The degenerative processes that occur during aging increase the risk of disease and impaired health. Meanwhile, interventions that target aging to promote healthy longevity are gaining interest, both academically and in the public. While nutritional and physical interventions exist, efficacy is often difficult to determine. It is therefore imperative that an aging score measuring the biological aging process is available to the wider public. However, simple, interpret, and accessible biological aging scores are lacking. Here, we developed PhysiAge, a physiological aging score based on five accessible parameters that have influence on or reflect the aging process: (1) average daily step count, (2) blood glucose, (3) systolic blood pressure, (4) sex, and (5) age. Here, we found that compared to calendar age alone, PhysiAge better predicts mortality, as well as established muscle aging markers such as decrease in NAD+ levels, increase in oxidative stress, and decline in physical functioning. In order to demonstrate the usefulness of PhysiAge in identifying relevant factors associated with decelerated aging, we calculated PhysiAges for a cohort of aged individuals and obtained mass spectrometry-based blood plasma metabolomic profiles for each individual. Here, we identified a metabolic signature of decelerated aging, which included components of the TCA cycle, including malate, citrate, and isocitrate. Higher abundance of these metabolites was associated with decelerated aging, in line with supplementation studies in model organisms. PhysiAge represents an accessible way for people to track and intervene in their aging trajectories, and identifies a metabolic signature of decelerated aging in human blood plasma, which can be further studied for its causal involvement in human aging.
| S-EPMC10643795 | biostudies-literature
Project description:The study characterises vascular phenotypes of hypertensive patients utilising machine learning approaches. Newly diagnosed and treatment-naïve primary hypertensive patients without co-morbidities (aged 18-55, n = 73), and matched normotensive controls (n = 79) were recruited (NCT04015635). Blood pressure (BP) and BP variability were determined using 24 h ambulatory monitoring. Vascular phenotyping included SphygmoCor® measurement of pulse wave velocity (PWV), pulse wave analysis-derived augmentation index (PWA-AIx), and central BP; EndoPAT™-2000® provided reactive hyperaemia index (LnRHI) and augmentation index adjusted to heart rate of 75bpm. Ultrasound was used to analyse flow mediated dilatation and carotid intima-media thickness (CIMT). In addition to standard statistical methods to compare normotensive and hypertensive groups, machine learning techniques including biclustering explored hypertensive phenotypic subgroups. We report that arterial stiffness (PWV, PWA-AIx, EndoPAT-2000-derived AI@75) and central pressures were greater in incident hypertension than normotension. Endothelial function, percent nocturnal dip, and CIMT did not differ between groups. The vascular phenotype of white-coat hypertension imitated sustained hypertension with elevated arterial stiffness and central pressure; masked hypertension demonstrating values similar to normotension. Machine learning revealed three distinct hypertension clusters, representing 'arterially stiffened', 'vaso-protected', and 'non-dipper' patients. Key clustering features were nocturnal- and central-BP, percent dipping, and arterial stiffness measures. We conclude that untreated patients with primary hypertension demonstrate early arterial stiffening rather than endothelial dysfunction or CIMT alterations. Phenotypic heterogeneity in nocturnal and central BP, percent dipping, and arterial stiffness observed early in the course of disease may have implications for risk stratification.
| S-EPMC9758678 | biostudies-literature
Project description:In Caenorhabditis elegans (C. elegans), ablation of germline stem cells (GSCs) leads to infertility, which extends lifespan. It has been reported that aging and reproduction are both inextricably associated with metabolism. However, few studies have investigated the roles of polar small molecules metabolism in regulating longevity by reproduction. In this work, we combined the nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to profile the water-soluble metabolome in C. elegans. Comparing the metabolic fingerprint between two physiological ages among different mutants, our results demonstrate that aging is characterized by metabolome remodeling and metabolic decline. In addition, by analyzing the metabolic profiles of long-lived germline-less glp-1 mutants, we discovered that glp-1 mutants regulate the levels of many age-variant metabolites to attenuate aging, including elevated concentrations of the pyrimidine and purine metabolism intermediates and decreased concentrations of the citric acid cycle intermediates. Interestingly, by analyzing the metabolome of daf-16;glp-1 double mutants, our results revealed that some metabolic exchange contributing to germline-mediated longevity was mediated by transcription factor FOXO/DAF-16, including pyrimidine metabolism and the TCA cycle. Based on a comprehensive metabolic analysis, we provide novel insight into the relationship between longevity and metabolism regulated by germline signals in C. elegans.
| S-EPMC5361674 | biostudies-literature
Project description:Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of severe PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH in its later stage, which may differ from the earlier stage of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH. Global profiles were determined in human lung tissue and compared across 11 normal and 12 severe pulmonary arterial hypertension patients. Using a combination of microarray and high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung.
2014-11-14 | E-GEOD-53408 | biostudies-arrayexpress
Project description:Aging is associated with a high prevalence of hypertension due to elevated susceptibility of BP to dietary salt, but its mechanism is unknown. Serum levels of Klotho, an anti-aging factor, decline with age. We found that high salt (HS) increased BP in aged mice and young heterozygous Klotho-knockout mice and was associated with increased vascular expression of Wnt5a and p-MYPT1, which indicate RhoA activity. Not only the Wnt inhibitor LGK974 and the Wnt5a antagonist Box5 but Klotho supplementation inhibits HS-induced BP elevation, similarly to the Rho kinase inhibitor fasudil, associated with reduced p-MYPT1 expression in both groups of mice. In cultured vascular smooth muscle cells, Wnt5a and angiotensin II (Ang II) increased p-MYPT1 expression but knockdown of Wnt5a with siRNA abolished Ang II-induced upregulation of p-MYPT1, indicating that Wnt5a is indispensable for Ang II-induced Rho/ROCK activation. Notably, Klotho inhibited Wnt5a- and Ang II-induced upregulation of p-MYPT1. Consistently, Klotho supplementation ameliorated HS-induced augmentation of reduced renal blood flow (RBF) response to intra-arterial infusion of Ang II and the thromboxane A2 analog U46619, which activated RhoA in both groups of mice and were associated with the inhibition of BP elevation, suggesting that abnormal response of RBF to Ang II contributes to HS-induced BP elevation. Thus, Klotho deficiency underlies aging-associated salt-sensitive hypertension through vascular non-canonical Wnt5a/RhoA activation.
| S-EPMC7410076 | biostudies-literature