Metabolic pathways perturbed in brivanib‐associated hypertension
hypertension, Hypertension, hypertensive
HYPERTENSION, HYPERTENSION
Perturbed metabolites associated with TKI‐induced hypertension were submitted to pathway analysis to devise an understanding of the metabolic processes that drove our biomarker. Hypertension was associated with an increase in glucose, glucopyranose (the pyranose form of glucose), fructose, and mannose. While the elevated levels of glycolysis constituents could be a function of impaired glycolysis, they may also be a function of increased substrate availability. Lactic acid was notably increased in the absence of accelerated glycolysis.TKI‐induced hypertension had a distinct pattern of amino acid perturbations. The amino acids phenylalanine, serine, and threonine were elevated in hypertensive patients, while levels of asparagine and cysteine were decreased. TKI‐induced hypertension was associated with increased levels of urea, hydroxyurea, and glutamine. Increased conversion of glutamine to urea is thought to inhibit synthesis of arginine. Ornithine and asparaginine, precursors of arginine, were at low levels.Finally, increased levels of free fatty acid (FFA) hexadecanoic acid were found in association with TKI‐induced hypertension.