Metabolic hormones, nitric oxide signaling components, and inflammation markers crosstalk in coronary artery disease.

Abstract

Objectives: To assess the crosstalk between the serum levels of the metabolic hormones, NO-signaling components, and inflammation markers in patients with coronary artery disease (CAD) with 3-year follow-up.

Methods: A total of 218 included patients underwent coronary angiography and a phone survey with a 3-year follow-up, which included records of cardiovascular (CV) events. Gensini score was evaluated to quantify atherosclerosis. NO-synthases (NOS) were profiled by an Explorer antibody array (Full Moon Biosystems, USA). ELISA was used to assay NOS, endothelin-1, leptin, adiponectin, and cGAMP in the whole cohort. C-reactive protein (CRP), glucose, and insulin were measured according to a routine analysis. Serum NOx were measured spectrophotometrically under diet in a hospital setting. Spearman correlation analysis, ROC-analysis, and logistic regressions were used to evaluate the associations between analytes, Gensini score, and CV-events.

Results: Correlation analysis reveals a complex network in which leptin deficiency appears to be a central, unfavorable and independent factor linked to CV-events. A pathological cycle involved hormone levels, imbalanced NOS isoforms and endothelin, metabolic factors, and CRP as inflammation marker. The direct pro-atherogenic roles of glucose, insulin, and CRP, and the protective potential of adiponectin and NOx were revealed.

Conclusions: Atherosclerosis was linked to a decrease in NOx. Elevated NOS isoforms may compensate for impaired NOS activity in atherosclerosis. Specific changes in the levels of NOS and NOx may be linked to the signaling pathways contributing to atherosclerosis and point to the correction of these changes using exogenous nitrate as dietary supplement.