Immune Activation and Inflammation in Patients with Cardiovascular Disease Are Associated with Higher Phenylalanine to Tyrosine Ratios: The Ludwigshafen Risk and Cardiovascular Health Study. (10th February 2014)

• Record Type: Journal Article
• Authors: Murr, Christian; Grammer, Tanja B.; Meinitzer, Andreas; Kleber, Marcus E.; März, Winfried; Fuchs, Dietmar
• Other Names: Gietzen Dorothy Academic Editor.
• Is Part Of: Journal of amino acids. Volume 2014(2014)
• Publication Date: 2014-02-10
• Subjects: Amino acids -- Periodicals; Amino Acids; Amino acids; Electronic journals; Periodical; Periodicals; 612.015756
• DOI: 10.1155/2014/783730
• Languages: English
• ISSNs: 2090-0404

Abstract

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'st -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 ofP < 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.