title: Immune activation and inflammation in patients with cardiovascular disease are associated with higher phenylalanine to tyrosine ratios: the ludwigshafen risk and cardiovascular health study.
abstract: Higher serum neopterin is associated with increased mortality in patients with coronary artery disease (CAD). Preferentially Th1-type cytokine interferon- γ stimulates neopterin production by GTP cychlohydrolase I (GCH-I) in parallel in monocyte-derived macrophages and dendritic cells. In other cells, activation of GCH-I leads to the formation of 5,6,7,8-tetrahydrobiopterin (BH4), the necessary cofactor of amino acid hydroxylases like phenylalanine 4-hydroxylase (PAH). Serum concentrations of phenylalanine, tyrosine, neopterin, and high sensitivity C-reactive protein (hsCRP) were measured in 1196 patients derived from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort study among patients referred for coronary angiography. The phenylalanine to tyrosine ratio (Phe/Tyr) served as an estimate of phenylalanine hydroxylase (PAH) enzyme activity. Serum concentrations of phenylalanine and tyrosine and of Phe/Tyr did not differ between individuals with or without CAD (Welch's t-test: P = n.s.). Higher neopterin and hsCRP concentrations were observed in CAD patients compared to controls (P < 0.0001) and they correlated with Phe/Tyr (Spearman's rank correlation for neopterin: r s = 0.216 and hsCRP: r s = 0.122; both of P < 0.0001) concentrations. In conclusion, immune activation is associated with higher Phe/Tyr in CAD patients. Data indicates subnormal PAH activity which might be involved in the precipitation of neuropsychiatric symptoms in patients.
authors.affiliation: Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innrain 80, 6020 Innsbruck, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Murr
authors.affiliation: Medical Clinic V (Nephrology, Hypertensiology, Endocrinolgy, Diabetology, Rheumatology), Mannheim Medical Faculty, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Tanja B
authors.initials: TB
authors.lastname: Grammer
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8010 Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.affiliation: Medical Clinic V (Nephrology, Hypertensiology, Endocrinolgy, Diabetology, Rheumatology), Mannheim Medical Faculty, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.affiliation: Medical Clinic V (Nephrology, Hypertensiology, Endocrinolgy, Diabetology, Rheumatology), Mannheim Medical Faculty, University of Heidelberg, 68167 Mannheim, Germany ; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8010 Graz, Austria ; Synlab Services GmbH, Synlab Academy, 68259 Mannheim, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innrain 80, 6020 Innsbruck, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs