The Coronary Endothelial Injury And The Change Of Cardiac Renin-Angiotensin System In Patients With Angina

Background Coronary endothelial dysfunction is the initiation factor of coronary atherosclerosis(As). It also plays a critical role in the development and progression of the coronary artery disease(CAD). Recent studies show that functional renin-angiotensin system(RAS) exist in the cardiac tissue. AngiotensinⅡ(AngⅡ) produced by cardiac RAS demonstrates powerful bioactivity in accelerating the pathophysiological progress of As. The aim of this study was to investigate the coronary endothelial injury, the cardiac RAS, and their correlations with angiographic manifestation in patients with stable angina (SA) or unstable angina (UA).Methods The 20 patients with UA , 17 patients with SA and 18 patients excluding coronary heart disease (control) were studied. Blood samples were collected during percutaneous coronary intervention (PCI). To investigate the coronary endothelial injury, we measured the concentrations of nitric oxide (NO),endothelin (ET) and the number of circulating endothelial cells(CEC) in coronary sinus blood. The aorta-coronary sinus gradients of plasma renin activity(PRA) and AngⅡconcentration were also measured as cardiac PRA and cardiac AngⅡ. The coronary artery lesion was described by jeopardy score.Results 1. In coronary sinus blood of UA patients, NO concentration was 42.72±17.72μmol/L,ET concentration was 115.94±24.08pg/ml,CEC number was 11.7±2.0cells/0.9μl；In SA patients, they were 55.60±10.53μmol/L, 91.18±17.19pg/ml and 7.3±2.5cells/0.9μl respectively；While in controls, they were 75.59±21.16μmol/L, 56.74±9.48pg/ml and 2.5±0.6cells/0.9μl respectively. Compared with control, the coronary endothelium was obviously injured in angina patients, especially in UA patients(P<0.01 or P<0.05); 2. In UA patients, the cardiac PRA was 0.77±0.60 ng/ml·h,the cardiac AngⅡconcentration was 47.09±42.40 pg/ml；In SA patients, they were 0.43±0.24 ng/ml·h and 18.57±6.50pg/ml respectively；While in controls, they were 0.13±0.45 ng/ml·h and 0.69±9.11pg/ml respectively. Compared with control, the cardiac RAS was activatedobviously in angina patients, especially in UA patients(P<0.01 or P<0.05); 3. The coronary endothelial injury and dysfunction showed a positive correlation with the activation of cardiac AngⅡ: the cardiac AngⅡ concentration showed a negative correlation with the coronary NO concentration(UA:γ=－0.615,P<0.01;SA:γ=－0.627,P<0.01),a positive correlation with the coronary ET concentration(UA:γ=0.803,P<0.01；SA:γ=0.873,P<0.01),and a positive correlation with the coronary CEC number(UA:γ=0.734,P<0.01；SA:γ=0.944,P<0.01)；4. The coronary endothelial injury and the cardiac AngⅡcorrelated with jeopardy score closely: the coronary NO concentration showed a negative correlation with the jeopardy score(UA:γ=－0.665,P<0.01；SA:γ=－0.570,P<0.01),the coronary ET concentration showed a positive correlation with the score(UA:γ=0.901,P<0.01；SA:γ=0.901,P<0.01), and the coronary CEC number showed also a positive correlation with the score(UA:γ=0.868,P<0.01；SA:γ=0.807,P<0.01)；The cardiac AngⅡ concentration correlated with the jeopardy score positively(UA:γ=0.888,P<0.01；SA:γ=0.656,P<0.01)。Conclusions 1. Compared with control, the coronary endothelium is injured and the cardiac RAS is activated obviously in angina patients, especially in UA patients; 2. The coronary endothelial injury and the activation of cardiac RAS may affect each other. This may cause a vicious cycle and result in the continuous lesion of coronary artery; 3. The coronary endothelial injury is not only the initiation factor, but a key role in the progression of As and CAD; 4. The activation of cardiac RAS plays as an aggravating factor in the pathophysiological progress of As and CAD; 5. Coronary angiography combined with detection of coronary endothelial injury and cardiac AngⅡ may better describe the lesion of coronary artery, and may better evaluate the prognosis of patients with CAD.