angiogenin and Acute-Coronary-Syndrome

It was the aim of this study to determine plasma haemoxygenase-1 (HO-1) across the spectrum of health, angina but normal coronary arteries (NCA), stable coronary artery disease (CAD), and acute coronary syndromes (ACS), and relationships with angiogenin, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1, and vascular endothelial growth factor. Plasma markers were measured (ELISA) in peripheral venous citrated plasma from 50 healthy subjects, 30 with NCA, 70 with stable CAD and 24 with an ACS, and from patient's aortic root, coronary ostium, coronary sinus and femoral artery. Human umbilical vein endothelial cells (HUVECs) were cultured with or without tumour necrosis factor (TNF), and platelets were probed. HO-1 was raised in stable CAD (p<0.05) and increased further in ACS (p<0.01) compared to healthy controls and NCA. HO-1 correlated only with MMP-9, and then only in the healthy controls. There were no major differences from cardiac or peripheral sites. HO-1 was present in HUVECs and 24-hour HUVEC supernatants but release was abolished by TNF. Platelets had no HO-1. In conclusion, HO-1 is raised in stable CAD and ACS and may arise from the endothelium but not the platelet. This may have implications for our understanding of the pathophysiology of CAD and its acute presentation as ACS.

Topics: Acute Coronary Syndrome; Aged; Angina Pectoris; Biomarkers; Blood Platelets; Cells, Cultured; Coronary Artery Disease; Cross-Sectional Studies; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Female; Heme Oxygenase-1; Humans; Linear Models; Male; Matrix Metalloproteinase 9; Middle Aged; Ribonuclease, Pancreatic; Time Factors; Tissue Inhibitor of Metalloproteinase-1; Tumor Necrosis Factor-alpha; Up-Regulation; Vascular Endothelial Growth Factor A

Angiogenin is a member of the ribonuclease superfamily, which has been implicated as a mitogen of endothelial cells and activator of matrix metalloproteinases and plasminogen-activated plasmin pathways. We hypothesized abnormalities of angiogenin levels in acute coronary syndrome (ACS), with prognostic implications for predicting adverse events.. We measured plasma angiogenin levels (ELISA) in 396 consecutive patients (63.4% males; mean age 67 years, SD 13) admitted with ACS, who were compared with 44 'disease controls' (patients with stable coronary artery disease) and 76 healthy controls. Clinical follow-up at 6 months was performed for adverse endpoints (cardiovascular death, recurrent ACS, revascularization and heart failure). ACS patients had significantly elevated plasma angiogenin levels compared with both disease controls and healthy controls (P < 0.001). After adjusting for baseline characteristics, raised troponin T levels and electrocardiographic changes, raised angiogenin levels were independently associated with more adverse events at 6 months' follow-up [HR 1.44 (95% CI: 1.10-1.89); P = 0.008].. Plasma angiogenin levels are significantly increased in ACS, and may be involved in the pathogenesis of this condition. High angiogenin levels were predictive of adverse events during follow-up.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Prognosis; Ribonuclease, Pancreatic; Troponin T; Vascular Endothelial Growth Factor A