Abstract
IntroductionModifications of apolipoprotein A1 (Apo A-I), the primary protein of high density lipoprotein, are potential biomarkers of coronary artery disease (CAD) severity. Methionine sulfoxidation, tyrosine chlorination and variable-sized truncations of Apo A-I have been reported in the literature to inactivate HDL and promote inflammatory disease progression. We hypothesize that a single amino acid truncation of glutamate residue 243 in the C-terminus of Apo A-I (Apo A-I Des-Q243) is a pathologic byproduct of a protease and it is associated with both the presence and the severity of coronary artery disease and chronic kidney disease (CKD).MethodsWe enrolled 103 patients presenting for evaluation of chest pain in this single-center cross-sectional study. Plasma and serum samples were gathered and processed for analysis of intact Apo A-I by high pressure liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS). Statistical analysis included a spearman’s coefficient, two-tailed linear regression and multivariate analysis of the relative fractional abundance (RFA) of Apo A-I Des-Q243 and clinical variables.ResultsMultivariate analysis revealed significantly increased levels of Apo A-I Des-Q243 in the presence of CKD (2.3%, P=0.037) and the presence of four (9.6%, P=0.005) or five (4.7%, P=0.045) coronary stents, regardless of vessel location. Angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (ACEI/ARB) (-2.4%, P=0.001), was associated with significantly reduced levels of Apo A-I Des-Q243. Finally, spearman’s coefficient demonstrated a negative correlation between estimated glomerular filtration rate (eGFR) and Apo A-I Des-Q243 (Plasma ρ=-0.024, P=0.014, Serum ρ=-0.291, P=0.003).ConclusionApo A-I Des-Q243 is elevated in patients with multiple coronary stents, and may be contributing to vascular inflammation and plaque formation. Furthermore, Apo A-I Des-Q243 is elevated in CKD and is directly correlated with its severity, as measured by eGFR. These findings suggest renin-aldosterone system (RAS) involvement in HDL modification and a protective action of ACEI/ARBs. Apo A-I Des-Q243 appears to be promising biomarker linking CAD and CKD that warrants further study.