Plasma concentrations of the cardiovascular risk factor asymmetric dimethylarginine (ADMA) are increased in patients with HIV-1 infection and correlate with immune activation markers

Kurz, Katharina; Teerlink, Tom; Sarcletti, Mario; Weiss, Günter; Zangerle, Robert; Fuchs, Dietmar

doi:10.1016/j.phrs.2009.07.009

Cited by 29 publications

(37 citation statements)

References 43 publications

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“…ADMA levels are elevated in the setting of HIV infection [18,19] independent of traditional cardiovascular risk factors, and the degree of elevation reflects the extent of HIV-associated inflammation as indicated by the CD4 + T-cell count and HIV RNA level [20]. Additionally, baseline levels of D-dimer, high sensitivity C-reactive protein (hsCRP), and IL-6 are associated with increased cardiovascular risk among HIV-infected individuals [21].…”

Section: Introductionmentioning

confidence: 99%

Increased levels of asymmetric dimethylarginine are associated with pulmonary arterial hypertension in HIV infection

Parikh

Scherzer

Nitta

et al. 2014

Aids

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Objective To examine the relationship between asymmetric dimethylarginine (ADMA) and HIV-associated pulmonary arterial hypertension (PAH). Design HIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. Chronic inflammation resulting in nitric oxide-mediated endothelial dysfunction is a key mechanism underlying other types of PAH. ADMA is an endogenous inhibitor of endothelial nitric oxide synthase. Among uninfected individuals, ADMA is associated with PAH and predicts disease-related mortality. Methods We measured ADMA, high sensitivity C-reactive protein, interleukin-6 (IL-6), D-dimer, and pulmonary artery systolic pressure (PASP) using echocardiography in HIV-infected individuals. Right heart catheterization (RHC) was performed in individuals with a PASP at least 30 mmHg. We performed multivariable analysis to identify factors associated with high PASP by echocardiogram and PAH by RHC. Results Among 214 HIV-infected individuals, the median age was 50 years, 82% were men, 71% were on antiretroviral therapy, and 4.2% carried a prior diagnosis of PAH. ADMA and IL-6 were associated with increased values of PASP following multivariable adjustment (7.2% per 0.1 μmol/l, P =0.0049 and 3.9% per doubling, P =0.027, respectively). In adjusted analysis among the 85 participants who underwent RHC, ADMA and IL-6 were associated with higher values of mean PAP (14.2% per 0.1 μmol/l, P =0.0014 and 5.8% per doubling, P =0.038, respectively). However, only ADMA was associated with PAH (prevalence ratio =1.74, P =0.029). Conclusion Elevated levels of ADMA are independently associated with PAH among HIV-infected individuals. Our findings suggest that chronic HIV-associated inflammation leading to an accumulation of ADMA and subsequent nitric oxide-mediated endothelial dysfunction may represent a novel mechanism for HIV-associated PAH.

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Section: Introductionmentioning

confidence: 99%

Increased levels of asymmetric dimethylarginine are associated with pulmonary arterial hypertension in HIV infection

Parikh

Scherzer

Nitta

et al. 2014

Aids

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“…ADMA has long been found to be associated with renal failure [20,21] and cardiovascular disease [22,23]. However, we recently reported increased levels of ADMA in asthma and cystic fibrosis airways [3–5], which likely contributes to NO imbalance and respiratory dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Dimethylarginine in Chronic Obstructive Pulmonary Disease (ADMA in COPD)

Scott

Duongh

Young

et al. 2014

IJMS

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l-Arginine metabolism including the nitric oxide (NO) synthase and arginase pathways is important in the maintenance of airways function. We have previously reported that accumulation of asymmetric dimethylarginine (ADMA) in airways, resulting in changes in l-arginine metabolism, contributes to airways obstruction in asthma and cystic fibrosis. Herein, we assessed l-arginine metabolism in airways of patients with chronic obstructive pulmonary disease (COPD). Lung function testing, measurement of fractional exhaled NO (FeNO) and sputum NO metabolites, as well as quantification of l-arginine metabolites (l-arginine, l-ornithine, l-citrulline, ADMA and symmetric dimethylarginine) using liquid chromatography-mass spectrometry (LC-MS) were performed. Concentrations of l-ornithine, the product of arginase activity, correlated directly with l-arginine and ADMA sputum concentrations. FeNO correlated directly with pre- and post-bronchodilator forced expiratory volume in one second (FEV1). Sputum arginase activity correlated inversely with total NO metabolite (NOx) and nitrite concentrations in sputum, and with pre- and post-bronchodilator FEV1. These findings suggest that ADMA in COPD airways results in a functionally relevant shift of l-arginine breakdown by the NO synthases towards the arginase pathway, which contributes to airway obstruction in these patients.

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“…Similar findings are also seen in asthma and cystic fibrosis (18)(19)(20)(21)(22)(23)(24)(25). Chronic obstructive pulmonary disease (COPD) is characterized by obstruction of the airways and progressive airway restriction (22).…”

Section: Discussionmentioning

confidence: 59%

Association between Newly Diagnosed Essential Hypertension, Smoking, Assymetric Dimethylarginine and ischemia-Modified Albumin

Altuntaş¹,

Bengü²,

Kiraz³

et al. 2017

Istanbul Med J

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Essential hypertension (HT) is one of the major reasons for admission to hospitals worldwide; it is a preventable and curable disease. In case of long-term exposure, clinical pictures such as renal failure, heart failure, and blindness can occur (1).Because the endothelium is a vascular layer that has very important roles in the maintenance of normal vascular functions, its dysfunction leads to many diseases of the cardiovascular system. One of the important molecules that regulate endothelial functions is nitric oxide (NO). NO deficiency can cause endothelial dysfunction and many diseases, particularly cardiovascular disease (2). Asymmetric dimethylarginine (ADMA) is an endogenous NO synthase (NOS) inhibitor. It inhibits local NO synthesis and causes endothelial dysfunction. It is considered as a risk factor for the development of coronary artery disease and essential HT (3).Ischemia-modified albumin (IMA) is a molecule that emerges due to a series of structural changes in the amino-terminal end binding metals in serum albumin (4). Its level increases due to oxidative stress, and one of the reasons for this increase is acute coronary syndrome (5).Smoking triggers many inflammatory disorders, particularly pulmonary diseases characterized by a progressive restriction in the airways. Although this process has not been clearly explained yet, it affects the extrapulmonary system (6).This study aimed to investigate the relationship between oxidative stress and increasing ADMA and IMA levels in patients with newly diagnosed HT and a history of smoking. MethodsThis study included 95 consecutive patients who presented to the outpatient clinic for any reason. The patients were divided into three groups: those who were healthy and non-smokers (Group 1, n=25), those who had left ventricular hypertrophy (LVH) accompanying newly diagnosed HT and were smokers (Group 2, n=35), and those who had LVH accompanying newly diagnosed HT Association between Newly Diagnosed Essential Hypertension, Smoking, Assymetric Dimethylarginine and ischemia-Modified AlbuminObjective: This study aimed to investigate the relationship between increasing levels of assymetric dimethylarginine (ADMA)and ischemia-modified albumin (IMA) in people with early diagnosis of hypertension (HT) and smoking history. Methods:The study included 95 outpatients who visited our hospital. Patients were classified into three groups: group 1, healthy and non-smokers (n=25); group 2, no smoker patients with newly diagnosed essential HT with LVH (left ventricle hypertrophia) (n=35); group 3, smoking patients with a LVH accompanying newly diagnosed essential HT (n=35). 51% of patients are females; 49% of them are males.The trial was approved by the local ethics committee. Blood samples were analyzed, which were taken after 8 h of fasting. Biochemical parameters such as, C reactive protein (CRP), ADMA, IMA values were recorded. Using echocardiography, cardiac values were recorded. Results:In this study, the first group consisted of 25 patients and second and third group of ...

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Plasma concentrations of the cardiovascular risk factor asymmetric dimethylarginine (ADMA) are increased in patients with HIV-1 infection and correlate with immune activation markers

Cited by 29 publications

References 43 publications

Increased levels of asymmetric dimethylarginine are associated with pulmonary arterial hypertension in HIV infection

Increased levels of asymmetric dimethylarginine are associated with pulmonary arterial hypertension in HIV infection

Asymmetric Dimethylarginine in Chronic Obstructive Pulmonary Disease (ADMA in COPD)

Association between Newly Diagnosed Essential Hypertension, Smoking, Assymetric Dimethylarginine and ischemia-Modified Albumin

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