HMGB1 induces secretion of matrix vesicles which participate in microcalcification of atherosclerotic plaques

AIM: Early calcification of atherosclerotic plaques are colocalized with macrophage and high mobility group box 1( HMGB1),a cytokine associated with biomineralizing process under physiological and pathological conditions. Our study aims to evaluate whether HMGB1 induces ectopic mineralization via promoting the secretion of matrix vesicles( MVs) from macrophages. METHODS: HMGB1 was added to the medium of macrophages,the secretion of MVs in the supernatant was tested by flow cytometry analysis. The mineral deposition in calcifying medium was detected by Alizarin Red staining and von Kossa staining. Transmission electron microscopy showed the formation of hydroxyapatite crystals in MVs. Then we subcutaneous injection into mice with MVs to induce regional mineralization. RESULTS: HMGB1 significantly promoted secretion of MVs from macrophages as raveled by flow cytometry analysis. TNAP activity,considered as a marker of MVs maturation,was higher in HMGB1-induced MVs compared to the control-MVs. HMGB1-MVs also led to mineral deposition in an in vitro MVs-collagen mineralization model. Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization. Mechanistic experiments revealed that HMGB1 activated neutral sphingomyelinase 2( n SMase2) that involved the receptor for advanced glycation end products( RAGE) and p38MAPK( upstream of n SMase2). Inhibition of n SMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and mineral deposition. CONCLUSIONS: HMGB1 induces MVs secretion from macrophages at least in part,via the RAGE / p38 MAPK /n SMase2 signaling pathway. Our findings thus reveal a novel mechanism by which HMGB1 may participated in the early calcification of atherosclerotic plaques.

Relationship between intravascular ultrasound imaging features of coronary plaques and soluble CD105 level in patients with coronary heart disease

Plaque rupture with subsequent thrombus formation is the common pathophysiological substrate of acute coronary syndrome （ACS）. Moreno et al reported mat neovascularization as manifested by the localized appearance of microvessels is increased in ruptured plaques in the human aorta. Microvessel density is also increased in inflammatory lesions, with intraplaque hemorrhage and in thin-cap fibroatheromas. Microvessels at the base of the plaque are independently correlated with plaque rupture, suggesting a contributory role for neovascularization in the process of plaque rupture. Soluble CD105, a sensitive serum marker of neovascularization, is thought to be associated with cardiovascular disease. The purpose of this study was to assess the relationship between the level of soluble CD105 and the morphological plaques by intravascular ultrasound （IVUS） in patients with stable angina （SA） and those with unstable angina （UA） and whether soluble CD105 may serve as a non-invasive marker of coronary plaque destabilization.

A case of myocardial abscess induced by Staphylococcus aureus with typical electrocardiogram of acute myocardial infarction

To the editor： Myocardial abscess is a rare but serious and lifethreatening disease. It is difficult to differentiate between myocardial abscess and acute myocardial infarction （AMI）, especially in patient whose electrocardiograph （ECG） reveals a significant STelevation over the anterior wall.