Association of serum HMGB2 level with MACE at 1 mo of myocardial infarction: Aggravation of myocardial ischemic injury in rats by HMGB2 via ROS.

High-mobility group box (HMGB) family is related to inflammatory diseases. We investigated whether serum HMGB2 levels are related to myocardial infarction (MI) severity and major adverse cardiac events (MACE) during MI. We included 432 consecutive patients with ST-segment elevation myocardial infarction and 312 controls. Serum HMGB2 levels were significantly higher in MI patients than in controls. Increased HMGB2 levels were associated with MACE and negatively with ejection fraction in MI patients. HMGB2 was an independent determinant of MACE in logistic regression analysis. HMGB2 protein (10 µg) or saline was injected intramyocardially in MI rats, with or without coadministration of the NADPH oxidase inhibitor apocynin. After 72 h, pathological, echocardiographic, and hemodynamic examinations showed that HMGB2 increased infarct size and worsened cardiac function in MI rats. Moreover, HMGB2 administration enhanced reactive oxygen species (ROS) production, cell apoptosis, inflammation, and autophagosome clearance impairment, which were attenuated by coadministration of apocynin or knock down of receptor for advanced glycation end products (RAGE). In conclusion, increased serum HMGB2 levels are associated with MI severity and MACE at 1 mo. HMGB2 promotes myocardial ischemic injury in rats and hypoxic H9C2 cell damage via ROS provoked by RAGE.NEW & NOTEWORTHY We demonstrate that serum high-mobility group box 2 is associated with major adverse cardiac events at 1 mo in myocardial infarction patients. Mechanistically, high-mobility group box 2 promotes reactive oxygen species production via receptor for advanced glycation end products signaling in ischemic myocardium, thereby aggravating cell apoptosis, inflammation, and autophagosome clearance impairment. This study reveals that high-mobility group box 2 is a novel factor enhancing ischemic injury in myocardial infarction.

Association of decreased serum vasostatin-2 level with ischemic chronic heart failure and with MACE in 3-year follow-up: Vasostatin-2 prevents heart failure in myocardial infarction rats.

BACKGROUND: We investigated whether serum vasostatin-2 level is related to chronic heart failure (CHF) in patients with previous myocardial infarction (MI) and MACE in 3-year follow-up. The biological effect of vasostatin-2 on ischemic HF was evaluated in animal experiments. METHODS: After exclusion of the subjects not eligible, this study included 450 patients with CHF and previous MI, and 149 healthy controls. Serum vasostatin-2 level was analyzed. CHF patients were followed up for three years and major adverse cardiac events (MACE) were recorded, defined as reinfarction, target-vessel revascularization, cardiovascular death and refractory HF requiring hospitalizations. RESULTS: Notably, serum vasostatin-2 level was decreased in CHF patients than in controls, and significant difference was observed between CHF patients with MACE and those without (both P<0.05). Vasostatin-2 level was correlated with HF stages (Spearman's r=-0.288, P<0.05), LVEF (r=0.377, P<0.05) and pro-BNP level (r=-0.294, P<0.05). Multivariable logistic regression analysis suggested that vasostatin-2, conventional risk factors, severity of HF stages and LVEF were independently associated with MACE in CHF patients. Vasostatin-2 (100µg) or PBS was injected intraperitoneally every other day in MI rats, follow by echocardiography, hemodynamic analysis after 2months. Compared with PBS, vasostatin-2 treatment prevented ischemic HF in MI rats, accompanied with reduction of infarct size, remodeling, fibrosis and inflammation, mainly through inhibition of Rho, Wnt and TLR-4 pathways and modulation of renin-angiotensin system. CONCLUSION: Decreased serum vasostatin-2 level is associated with ischemic CHF and with MACE in three-year follow-up. Intraperitoneal injection of vasostatin-2 protects against ischemic HF in MI rats.

Mineral metabolism disturbances are associated with the presence and severity of calcific aortic valve disease.

OBJECTIVE: We investigated whether disturbance of calcium and phosphate metabolism is associated with the presence and severity of calcific aortic valve disease (CAVD) in patients with normal or mildly impaired renal function. METHODS: We measured serum levels of calcium, phosphate, alkaline phosphatase (AKP), intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-OHD), and biomarkers of bone turnover in 260 consecutive patients with normal or mildly impaired renal function and aortic valve sclerosis (AVSc) (n=164) or stenosis (AVS) (n=96) and in 164 age- and gender-matched controls. Logistic regression models were used to determine the association of mineral metabolism parameters with the presence and severity of CAVD. RESULTS: Stepwise increases were observed in serum levels of calcium, phosphate, AKP, and iPTH from the control group to patients with AVS, and with reverse changes for 25-OHD levels (all P<0.001). Similarly, osteocalcin, procollagen I N-terminal peptide, and ß-isomerized type I collagen C-telopeptide breakdown products were significantly increased stepwise from the control group to patients with AVS (all P<0.001). In patients with AVS, serum levels of iPTH were positively, in contrast 25-OHD levels were negatively, related to trans-aortic peak flow velocity and mean pressure gradient. After adjusting for relevant confounding variables, increased serum levels of calcium, phosphate, AKP, and iPTH and reduced serum levels of 25-OHD were independently associated with the presence and severity of CAVD. CONCLUSIONS: This study suggests an association between mineral metabolism disturbance and the presence and severity of CAVD in patients with normal or mildly impaired renal function. Abnormal bone turnover may be a potential mechanism.

[The impact of expansion of sirolimus eluting stent on intimal hyperplasia: an intravascular ultrasound study].

OBJECTIVE: To assess the impact of expansion grade of sirolimus eluting stent on intimal hyperplasia with intravascular ultrasound (IVUS). METHODS: A total of 75 patients implanted with sirolimus eluting stents for at least 8 months were enrolled in this study and IVUS could be performed in 76 stents of 73 patients and 2 patients were excluded due to total coronary occlusion. External elastic membrane (EEM) cross-sectional areas (CSA) at stent inlet and outlet, at in-stent minimal CSA; in-stent CSA, cavity CSA, intimal area (in-stent area-cavity area), maximal and minimal diameter of stent, and symmetry index of stent (minimal diameter of stent/maximal diameter of stent) were measured. RESULT: Five out of 76 stents of 73 patients developed intimal hyperplasia and intimal proliferation was inhibited by sirolimus eluting stent in patients with either minimal stent CSA/EEM CSA < 0.5 (n = 56) or >or= 0.5 (n = 20), minimal stent CSA/reference CSA < 0.9 (n = 44) or >or= 0.9 (n = 32), minimal stent CSA < 5 mm(2) (n = 25) or CSA >or= 5 mm(2) (n = 51), symmetry index of stent at minimal CSA of stent < 0.9 (n = 37) or >or= 0.9 (n = 39) during IVUS follow up. CONCLUSION: Sirolimus eluting stent inhibited intimal hyperplasia independent of stent expansion grade.

[Impact of coronary sirolimus-eluting stents on long-term outcome in diabetic patients].

OBJECTIVE: To analyse the impact of sirolimus-eluting stents (SES) on long-term outcomes in patients with coronary artery disease (CAD) and diabetes. METHODS: Among 1004 patients with CAD undergone percutaneous coronary intervention (PCI), 84 diabetic and 250 non-diabetic patients received SES, 168 diabetic and 502 non-diabetic patients had bare metal stent (BMS) implantation. Baseline clinical characteristics, interventional procedures (coronary angiography and PCI), occurrence of major adverse cardiac events (MACE), and MACE-free survival rates at one year during follow-up were compared. RESULTS: During follow-up (average 16.2 months), patients (with and without diabetes mellitus) who received SES had similar occurrence of MACE (4.8% vs. 3.6%, P = 0.744) and MACE-free survival rates at one year (95.0% vs. 96.7%, P = 0.602). However those received BMS had a higher occurrence of MACE in diabetes mellitus than that in non-diabetic patients (31.0% vs. 21.7%, P = 0.015). MACE-free survival rate at one year was lower in diabetic patients with BMS than that in non-diabetic patients with BMS (74.2% vs. 86.8%, P = 0.001). CONCLUSION: Implantation of sirolimus-eluting stents may reduce the major adverse cardiac events and the frequency of repeat intervention in patients with diabetes mellitus.