Abstract 9801: Increased High-Mobility Group Box1 Expression at Ruptured Plaque Was Associated with Microvascular Damage after Reperfusion in Patients with Myocardial Infarction
Background: Locally increased inflammatory response at the ruptured plaque contributes to no-reflow phenomenon. High-mobility group box1 (HMGB1) is a potent innate danger signal released from injured and activated immune cells, that initiates pro-inflammatory response. We hypothesized that culprit coronary artery of ST-elevation myocardial infarction (STEMI) contains an elevated level of HMGB1 that may play an adverse role on myocardial reperfusion.
Methods and Results: Fifty patients with reperfused STEMI and 35 patients with chronic stable angina (CSA) were examined. Local blood samples from the ruptured plaque were taken in patients with STEMI using aspiration catheterization. Systemic blood samples were taken from the aorta. Local and systemic serum HMGB1 level did not differ between presence or absence of atherosclerotic risk factors, prior use of cardiovascular medications, anterior infarction, collateral, and multivessel disease. Systemic level of HMGB1 was significantly higher in patients with STEMI than in patients with CSA (4.9±2.5 vs. 0.9±1.6 ng/ml, p<0.0001). In patients with STEMI, local serum HMGB1 level at the ruptured plaque was higher compared with systemic level (6.3±4.6 vs. 4.9±2.5 ng/ml, p<0.01). Local HMGB1 level, but not systemic HMGB1 level, was significantly increased in patients with final Thrombolysis In Myocardail Infarction (TIMI) <III (n=7) compared with final TIMI-III (n=43) (9.9±6.3 vs. 5.8±4.1 ng/ml, p<0.05). Among the patients with final TIMI-III, local HMGB1 level was elevated in patients with poor ST-resolution (<50%, n=14) compared with those with good ST-resolution (n=29) (8.2±6.1 vs. 4.8±2.5 ng/ml, p<0.05). Local HMGB1 level was higher in patients with pump failure and ventricular fibrillation/sustained ventricular tachycardia compared with those without (all p<0.05).
Conclusions: Serum HMGB1 level was increased not only in the systemic circulation, but also at the site of plaque rupture in patients with STEMI. Elevated HMGB1 level at the ruptured plaque was associated with no-reflow phenomenon, poor ST-resolution, and adverse clinical outcomes, suggesting that HMGB1 might be an important factor contributing to the development of microvascular damage after reperfusion in patients with STEMI.
- © 2011 by American Heart Association, Inc.