Serum concentrations of l-arginine and l-homoarginine in male patients with intermittent claudication: A cross-sectional and prospective investigation in the CAVASIC Study

Vogl, Lena; Pohlhammer, Johannes; Meinitzer, Andreas; Rantner, Barbara; Stadler, Marietta; Peric, Slobodan; Hammerer-Lercher, Angelika; Klein-Weigel, Peter; Fraedrich, Gustav; Kronenberg, Florian; Kollerits, Barbara

doi:10.1016/j.atherosclerosis.2015.02.019

Cited by 19 publications

(26 citation statements)

References 41 publications

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“…After evaluating the full-text documents of these 20 studies, 7 studies were excluded for the following reasons: 5 did not report specific all-cause mortality outcomes, 1 did not follow-up study participants for ≥6 months, and 1 measured homoarginine in urine but not in serum/plasma ( Figure 1). [24][25][26][27][28][29][30][31][32][33][34][35][36] Eight studies were conducted in participants with predominant cardiovascular disease, 25,27,29,30,32-35 4 were conducted in participants with predominant renal disease (chronic kidney disease or post-renal transplant), 24,28,31,36 whereas 1 investigated subjects with liver disease. Table 1 describes specific information of the 13 studies meeting the inclusion criteria and included in the meta-analyses.…”

Section: Resultsmentioning

confidence: 99%

“…[24][25][26][27][28][29][30][31][32][33][34][35][36] Eight studies were conducted in participants with predominant cardiovascular disease, 25,27,29,30,32-35 4 were conducted in participants with predominant renal disease (chronic kidney disease or post-renal transplant), 24,28,31,36 whereas 1 investigated subjects with liver disease. [26][27][28]30,[34][35][36] All studies were of high quality (Cohen Kappa's coefficient = 0.755). Survival data, presented either as Kaplan-Meier or as Nelson-Aalen curves, were provided in 8 studies.…”

Section: Resultsmentioning

confidence: 99%

“…Survival data, presented either as Kaplan-Meier or as Nelson-Aalen curves, were provided in 8 studies. [24][25][26]28,30,32,33,36 Homoarginine was measured in plasma in 7 studies 24,25,[29][30][31][32][33] and in serum in 6 studies, [26][27][28][34][35][36] using gas chromatographymass spectrometry in 1 study (GC-MS), 24 liquid chromatography-mass spectrometry (LC-MS) in 5 studies 25,29,[31][32][33] and liquid chromatography with fluorescent detection (LC-FLR) in 7 studies. [26][27][28]30,[34][35][36] All studies were of high quality (Cohen Kappa's coefficient = 0.755).…”

Section: Resultsmentioning

confidence: 99%

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Homoarginine and all‐cause mortality: A systematic review and meta‐analysis

Zinellu

Paliogiannis

Carru

et al. 2018

Eur J Clin Investigation

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This meta-analysis of observational studies showed an inverse association between circulating homoarginine concentrations and all-cause mortality. Further research is warranted to investigate the direct effects of homoarginine on cardiovascular homoeostasis, the associations between homoarginine and all-cause mortality in other population groups, and the effects of interventions on homoarginine concentrations on clinical outcomes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Homoarginine and all‐cause mortality: A systematic review and meta‐analysis

Zinellu

Paliogiannis

Carru

et al. 2018

Eur J Clin Investigation

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“…Plasma concentrations of homoarginine are inversely correlated with the risk of cardiovascular disease and overall mortality (Marz et al ; Jud et al ), increased risk for fatal strokes (Haghikia et al ), congestive heart failure and left ventricular hypertrophy (Atzler et al , , Pilz et al ; Bahls et al ), aging (Marz et al ; Atzler et al ), smoking (Zwan et al ; Sobczak et al ; Atzler et al ; Vogl et al ), body mass index (Marz et al ; Atzler et al ; Pilz et al ), and pregnancy (Valtonen et al ). In addition, the effects of homoarginine on nitric oxide (NO) synthesis have been linked with increased risk of stroke and atherosclerosis as a reduction in homoarginine levels increased the aortic intima‐media thickness (Haghikia et al ).…”

Section: Introductionmentioning

confidence: 99%

l ‐Homoarginine supplementation prevents diabetic kidney damage

et al. 2019

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l‐homoarginine is an endogenous, non‐proteinogenic amino acid that has emerged as a new player in health and disease. Specifically, low l‐homoarginine levels are associated with cardiovascular diseases, stroke, and reduced kidney function. However, the role of l‐homoarginine in the pathogenesis of diabetic nephropathy (DN) is not known. Experiments were conducted in 6‐week‐old Ins2Akita mice supplemented with l‐homoarginine via drinking water or mini osmotic pump for 12 weeks. Both plasma and kidney l‐homoarginine levels were significantly reduced in diabetic mice compared to nondiabetic controls. Untreated Ins2Akita mice showed significant increases in urinary albumin excretion, histological changes, glomerular macrophage recruitment, the inflammatory cytokine KC‐GRO/CXCL1, and urinary thiobarbituric acid reactive substances (TBARS) excretion as an indicator of oxidative stress, along with a significant reduction in kidney nitrate + nitrite levels compared to control mice at 18 weeks of age. In contrast, l‐homoarginine supplementation for 12 weeks in Ins2Akita mice, via either drinking water or mini osmotic pump, significantly reduced albuminuria, renal histological changes, glomerular macrophage recruitment, KC‐GRO/CXCL1 levels, urinary TBARS excretion, and largely restored kidney nitrate + nitrite levels. These data demonstrate that l‐homoarginine supplementation attenuates specific features of DN in mice and could be a potential new therapeutic tool for treating diabetic patients.

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“…Recent epidemiological studies have demonstrated an association between low circulating levels of the endogenous nonproteinogenic amino acid L-homoarginine and an increased risk of cardiovascular and cerebrovascular events123. Furthermore, low levels of homoarginine have been shown to correlate with all-cause mortality in patients referred for coronary angiography1, diabetic patients on hemodialysis1, patients with peripheral arterial disease4, heart failure5 or stroke6, and in renal transplant recepients7, as well as in the general population8. Dietary supplementation of homoarginine in rodents demonstrated that homoarginine may play a protective role in experimental models of cardiovascular and cerebrovascular diseases6910.…”

mentioning

confidence: 99%

A Novel Pathway for Metabolism of the Cardiovascular Risk Factor Homoarginine by alanine:glyoxylate aminotransferase 2

Rodionov

Oppici

Martens‐Lobenhoffer

et al. 2016

Sci Rep

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Low plasma concentrations of L-homoarginine are associated with an increased risk of cardiovascular events, while homoarginine supplementation is protective in animal models of metabolic syndrome and stroke. Catabolism of homoarginine is still poorly understood. Based on the recent findings from a Genome Wide Association Study we hypothesized that homoarginine can be metabolized by alanine:glyoxylate aminotransferase 2 (AGXT2). We purified human AGXT2 from tissues of AGXT2 transgenic mice and demonstrated its ability to metabolize homoarginine to 6-guanidino-2-oxocaproic acid (GOCA). After incubation of HepG2 cells overexpressing AGXT2 with isotope-labeled homoarginine-d4 we were able to detect labeled GOCA in the medium. We injected wild type mice with labeled homoarginine and detected labeled GOCA in the plasma. We found that AGXT2 knockout (KO) mice have higher homoarginine and lower GOCA plasma levels as compared to wild type mice, while the reverse was true for AGXT2 transgenic (Tg) mice. In summary, we experimentally proved the presence of a new pathway of homoarginine catabolism – its transamination by AGXT2 with formation of GOCA and demonstrated that endogenous AGXT2 is required for maintenance of homoarginine levels in mice. Our findings may lead to development of novel therapeutic approaches for cardiovascular pathologies associated with homoarginine deficiency.

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Serum concentrations of l-arginine and l-homoarginine in male patients with intermittent claudication: A cross-sectional and prospective investigation in the CAVASIC Study

Cited by 19 publications

References 41 publications

Homoarginine and all‐cause mortality: A systematic review and meta‐analysis

Homoarginine and all‐cause mortality: A systematic review and meta‐analysis

l ‐Homoarginine supplementation prevents diabetic kidney damage

A Novel Pathway for Metabolism of the Cardiovascular Risk Factor Homoarginine by alanine:glyoxylate aminotransferase 2

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