Metabolites and Hypertension: Insights into Hypertension as a Metabolic Disorder

Chakraborty, Saroj; Mandal, Juthika; Yang, Tao; Cheng, Xi; Yeo, Ji‐Youn; McCarthy, Cameron G.; Koch, Lauren G.; Hill, Jennifer W.; Vijay‐Kumar, Matam; Joe, Bina

doi:10.1161/hypertensionaha.120.13896

Cited by 38 publications

(23 citation statements)

References 231 publications

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“…Although it has not yet been proven whether inflammation in humans is causatively related to hypertension or represents a secondary effect of hypertension, it is nevertheless clear that inflammation and the dysregulated immune system are closely linked, and that immunoinflammation plays an important role in hypertension. 60 , 61 Several factors involved in hypertension including genetic susceptibility, 65 neurohumoral activation, 64 , 66 salt (sodium), 67 – 69 and gut microbiome 68 , 70 among others may promote immunoinflammation in hypertension. Notwithstanding the complexity of the interplay of these factors, it has been suggested that oxidative stress and increased generation of reactive oxygen species represent a common molecular basis linking immunoinflammation in hypertension.…”

Section: Impact Of Dysregulated Immunoinflammation In Hypertension Onmentioning

confidence: 99%

Hypertension, a Moving Target in COVID-19

Savoia

Volpe

Kreutz

2021

Circulation Research

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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associates with a considerable high rate of mortality and represents currently the most important concern in global health. The risk of more severe clinical manifestation of COVID-19 is higher in males and steeply raised with age but also increased by the presence of chronic comorbidities. Among the latter, early reports suggested that arterial hypertension associates with higher susceptibility to SARS-CoV-2 infection, more severe course and increased COVID-19–related deaths. Furthermore, experimental studies suggested that key pathophysiological hypertension mechanisms, such as activation of the renin-angiotensin system (RAS), may play a role in COVID-19. In fact, ACE2 (angiotensin-converting-enzyme 2) is the pivotal receptor for SARS-CoV-2 to enter host cells and provides thus a link between COVID-19 and RAS. It was thus anticipated that drugs modulating the RAS including an upregulation of ACE2 may increase the risk for infection with SARS-CoV-2 and poorer outcomes in COVID-19. Since the use of RAS-blockers, ACE inhibitors or angiotensin receptor blockers, represents the backbone of recommended antihypertensive therapy and intense debate about their use in the COVID-19 pandemic has developed. Currently, a direct role of hypertension, independent of age and other comorbidities, as a risk factor for the SARS-COV-2 infection and COVID-19 outcome, particularly death, has not been established. Similarly, both current experimental and clinical studies do not support an unfavorable effect of RAS-blockers or other classes of first line blood pressure lowering drugs in COVID-19. Here, we review available data on the role of hypertension and its management on COVID-19. Conversely, some aspects as to how the COVID-19 affects hypertension management and impacts on future developments are also briefly discussed. COVID-19 has and continues to proof the critical importance of hypertension research to address questions that are important for global health.

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Section: Impact Of Dysregulated Immunoinflammation In Hypertension Onmentioning

confidence: 99%

Hypertension, a Moving Target in COVID-19

Savoia

Volpe

Kreutz

2021

Circulation Research

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“…Primarily, these coenzymes regulate electron (e − ) exchange in essential metabolic processes and scavenging of intracellular ROS generated during the infectivity cycle. It is well established that metabolic stresses, including obesity, type 2 diabetes [36], smoking [37], heart failure [38], hypertension [39], nerve damage [40], and brain injury [41], deplete intracellular ATP and NAD+ in affected tissues with a dramatic induction of ROS and PARP-1 expression. Induced ROS levels also result in depleted NAD+ levels and an impaired antioxidant system, following inflammatory triggers (cytokine response and cellular activation/adhesion markers) that are hallmarks of aging, hypertension, diabetes, and obesity [42][43][44][45].…”

Section: Parp-1 In Viral Pathologymentioning

confidence: 99%

Therapeutic Significance of microRNA-Mediated Regulation of PARP-1 in SARS-CoV-2 Infection

Dash

Pandhare

2021

ncRNA

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The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 (2019-nCoV) has devastated global healthcare and economies. Despite the stabilization of infectivity rates in some developed nations, several countries are still under the grip of the pathogenic viral mutants that are causing a significant increase in infections and hospitalization. Given this urgency, targeting of key host factors regulating SARS-CoV-2 life cycle is postulated as a novel strategy to counter the virus and its associated pathological outcomes. In this regard, Poly (ADP)-ribose polymerase-1 (PARP-1) is being increasingly recognized as a possible target. PARP-1 is well studied in human diseases such as cancer, central nervous system (CNS) disorders and pathology of RNA viruses. Emerging evidence indicates that regulation of PARP-1 by non-coding RNAs such as microRNAs is integral to cell survival, redox balance, DNA damage response, energy homeostasis, and several other cellular processes. In this short perspective, we summarize the recent findings on the microRNA/PARP-1 axis and its therapeutic potential for COVID-19 pathologies.

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“…There are many metabolites reported to be associated with hypertension, including vasoactive metabolites (tryptophan and its derivatives), nitric oxide related metabolites (e.g. arginine, ADMA), microbiome-derived metabolites (short-chain fatty acids, trimethylamine-N-oxide), TCA cycle intermediates, ketone bodies, and bile acids 24 . While not all these metabolites were associated with hypertensive status in our cohort, we did see several biologically-plausible associations.…”

Section: Resultsmentioning

confidence: 99%

A hierarchical approach to removal of unwanted variation for large-scale metabolomics data

et al. 2021

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Liquid chromatography-mass spectrometry-based metabolomics studies are increasingly applied to large population cohorts, which run for several weeks or even years in data acquisition. This inevitably introduces unwanted intra- and inter-batch variations over time that can overshadow true biological signals and thus hinder potential biological discoveries. To date, normalisation approaches have struggled to mitigate the variability introduced by technical factors whilst preserving biological variance, especially for protracted acquisitions. Here, we propose a study design framework with an arrangement for embedding biological sample replicates to quantify variance within and between batches and a workflow that uses these replicates to remove unwanted variation in a hierarchical manner (hRUV). We use this design to produce a dataset of more than 1000 human plasma samples run over an extended period of time. We demonstrate significant improvement of hRUV over existing methods in preserving biological signals whilst removing unwanted variation for large scale metabolomics studies. Our tools not only provide a strategy for large scale data normalisation, but also provides guidance on the design strategy for large omics studies.

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Metabolites and Hypertension: Insights into Hypertension as a Metabolic Disorder

Cited by 38 publications

References 231 publications

Hypertension, a Moving Target in COVID-19

Hypertension, a Moving Target in COVID-19

Therapeutic Significance of microRNA-Mediated Regulation of PARP-1 in SARS-CoV-2 Infection

A hierarchical approach to removal of unwanted variation for large-scale metabolomics data

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