oqiang Gu

Atorvastatin protects vascular smooth muscle cells from TGF-β1-stimulated calcification by inducing autophagy via suppression of the β-catenin pathway.

Background: Arterial calcification is a major event in the progression of atherosclerosis. It is reported that statins exhibit various protective effects against vascular smooth muscle cell (VSMC) inflammation and proliferation in cardiovascular remodeling. Although statins counteract atherosclerosis, the molecular mechanisms of statins on the calcium release from VSMCs have not been clearly elucidated. Methods: Calcium content of VSMCs was measured using enzyme-linked immunosorbent assay (ELISA). The expression of proteins involved in cellular transdifferentiation was analyzed by western blot. Cell autophagy was measured by fluorescence microscopic analysis for acridine orange staining and transmission electron microscopy analysis. The autophagic inhibitors (3-MA, chloroquine, NH4Cl and bafilomycin A1) and β-catenin inhibitor JW74 were used to assess the effects of atorvastatin on autophagy and the involvement of β-catenin on cell calcification respectively. Furthermore, cell transfection was performed to overexpress β-catenin. Results: In VSMCs, atorvastatin significantly suppressed transforming growth factor-β1 (TGF-β1)-stimulated calcification, accompanied by the induction of autophagy. Downregulation of autophagy with autophagic inhibitors significantly suppressed the inhibitory effect of atorvastatin on cell calcification. Moreover, the beneficial effect of atorvastatin on calcification and autophagy was reversed by β-catenin overexpression. Conversely, JW74 supplement enhanced this effect. Conclusion: These data demonstrated that atorvastatin protect VSMC from TGF-β1-stimulated calcification by inducing autophagy through suppression of the β-catenin pathway, identifying autophagy induction might be a therapeutic strategy for use in vascular calcification.

Low-Dose Furosemide Administered with Adequate Hydration Reduces Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography

Objective: We investigated the effects of low-dose furosemide, administered with adequate hydration on contrast-induced nephropathy (CIN). Methods: A total of 859 patients scheduled to undergo coronary angiography or angioplasty were enrolled and randomly assigned to a furosemide treatment or control group. All patients received supplemental hydration. Immediately after surgery, patients in the furosemide group received intravenous furosemide injection (20 mg); those in the control group received no treatment. Total fluid intake and urine output were recorded. Pre- and postsurgical changes in serum creatinine levels (SCr), glomerular filtration rate (GFR) and creatinine clearance rate (CCr) were assessed, and the incidence of CIN was also evaluated between the two groups. Logistic regression analysis was used to study risk factors for CIN. Results: General baseline conditions were similar between the two groups. Patients who received furosemide had significantly less increase in SCr and a more marked increase in GFR and CCr than those who did not. The incidence of CIN was significantly higher in the control group. Logistic regression analysis revealed that female gender and angiotensin-converting enzyme inhibitor were risk factors for CIN, whereas furosemide acted as a protective agent. Conclusions: With full hydration, small doses of furosemide can reduce CIN better than hydration alone.

Cardioprotective effects of single oral dose of nicorandil before selective percutaneous coronary intervention

Objective: Nicorandil, an opener of ATP-sensitive K+ channels, was used to treat angina in patients with coronary artery disease. In this study, we aim to investigate the cardioprotective effects of single oral dose of nicorandil in patients undergoing selective percutaneous coronary intervention (PCI). Methods: One hundred and thirty-eight patients with acute coronary syndrome undergoing PCI from July 2011 to October 2012 were randomly divided into control group (group 1, n=47), 10 mg oral nicorandil group (group 2, n=45), and 20 mg oral nicorandil group (group 3, n=46) about 2 hours before procedure, respectively. Cardiac troponin I (cTnI) levels were determined at 20 ~ 24 hours after PCI. Results: There was a significant difference in the rate of any cTnI elevation among the three groups (group 1: 36.17%, group 2: 20.00%, group 3: 15.22%, p=0.0176). With respect to the frequency of cTnI elevation ≥3 and 5×the upper limit of normal (ULN), there also had statistical difference among the three groups (17.02% in group 1, 8.89% in group 2, and 4.35% in group 3, respectively for cTnI elevation ≥3× ULN, p=0.0428; 12.77% in group 1, 6.67% in group 2, and 2.17% in group 3, respectively, for cTnI elevation ≥5× ULN, p=0.0487). Logistic regression analysis showed that LVEF (OR=0.915, 95% CI=0.853-0.981) and the use of nicorandil (OR=0.516, 95% CI=0.267-0.996) before PCI were independent protective factors of myocardial injury. Conclusion: Single oral dose of nicorandil (10 mg, 20 mg) 2 hours before the PCI procedure could decrease the incidence of peri-procedure myocardial injury and PCI-related myocardial infarction.

The effect of dalteparin versus unfractionated heparin on the levels of troponin I and creatine kinase isoenzyme MB in elective percutaneous coronary intervention: a multicenter study.

BackgroundThe aim of this study was to investigate the safety and efficacy of dalteparin during an elective percutaneous coronary intervention (PCI) procedure in a large cohort. Materials and methodsIn this prospective, randomized, open-label design study, 733 patients undergoing elective PCI were divided into an unfractionated heparin group (group 1, 323 patients) or a dalteparin group (group 2, 410 patients). Blood samples were collected before and 18–24 h after the PCI procedure to determine the serum levels of cardiac troponin I (cTnI) and creatine kinase isoenzyme MB. Major adverse cardiac events (MACEs) and bleeding events during hospitalization were also recorded. Patients with an increased level of serum cTnI before PCI were excluded from the study. ResultsAfter PCI, the cTnI values were greater than three times the upper limit of normal in 43 cases (13.3%) in group 1 and 52 cases (12.7%) in group 2, without a statistically significant difference between the two groups (P=0.801). An increased creatine kinase isoenzyme MB level of greater than two times the upper limit of normal was found in 10 cases (3.1%) in group 1 and 12 cases (2.9%) in group 2, without a statistically significant difference between the two groups (P=0.894). Postoperative bleeding was observed in nine patients (2.8%) in group 1 and six patients (1.5%) in group 2. Postoperative MACEs were observed in two patients (0.6%) in group 1 and two patients (0.5%) in group 2. There were no significant differences between the two groups with respect to bleeding events or MACEs. ConclusionOur study showed that dalteparin might be as effective and safe as unfractionated heparin for anticoagulation during elective PCI.

Fractional systolic and diastolic pressures act as predictors of coronary artery disease

Aims. This study was designed to determine if fractional systolic/diastolic pressures act as predictors of the extent of coronary artery disease. Patients and methods. A total of 545 consecutive patients (305 men, 240 women, with mean age 54.2 years) were involved in the study. The patients were diagnosed with coronary and non-coronary artery disease confirmed by angiography. Results. 353 patients were confirmed to have coronary artery disease, with 134 cases involving one vessel, 101 two vessels and 118 three vessels. There were significant differences between brachial and ascending aortic systolic blood pressures, fractional systolic blood pressures and fractional diastolic blood pressures in the patients with coronary artery disease compared with patients with non-coronary artery disease. Blood pressure measured in the brachial artery was higher than the pressure measured in the ascending artery. Ascending aortic fractional systolic/diastolic pressures were associated with coronary Gensini score, and were significantly related to the number of diseased vessels. Conclusions. Fractional systolic and diastolic pressures in the ascending aorta were strong predictive factors for the extent of coronary artery disease. Central pressures measured invasively in the ascending aorta were more predictive than peripheral pressures for the evaluation of coronary artery disease.

Impact of baseline blood pressure on the magnitude of blood pressure lowering by nifedipine gastrointestinal therapeutic system: refreshing the Wilder’s principle

Background The objective of the study was to investigate the relationship between baseline blood pressure (BP) and the magnitude of BP reduction in patients with essential hypertension treated with nifedipine gastrointestinal therapeutic system (NGTS). Methods and patients One hundred and thirty-eight patients with essential hypertension were enrolled in this prospective, single-arm, open-label study. NGTS was administered for 24 weeks to achieve target BP of 140/90 mmHg. The dose could be uptitrated to 60 mg/d in case of unsatisfactory BP reduction after 4-week treatment. Home blood pressure measurement was recorded through the initial 1–14 days, and office BP and heart rate were evaluated at 2, 4, 8, 12, and 24 weeks. Results One hundred and seventeen patients (84.8%) completed the study, and their average BP decreased by 19.0/11.3 mmHg after 24 weeks. The reduction of either systolic or diastolic BP was positively correlated with baseline BP at weeks 2, 4, or 24 after treatment (r=0.603–0.762, all p<0.05). The maximal BP reduction was observed in 83% of patients at 4 weeks of treatment even though the dose of nifedipine remained unchanged (30 mg/day). Conclusion These findings show that BP reduction is greatly influenced by the baseline level. Patients with high baseline BP had maximum reduction after treatment with NGTS, and the maximal antihypertensive efficacy of NGTS could appear even at 4 weeks after treatment initiation.

Early intervention of long-acting nifedipine GITS reduces brachial–ankle pulse wave velocity and improves arterial stiffness in Chinese patients with mild hypertension: a 24-week, single-arm, open-label, prospective study

Background Nifedipine gastrointestinal therapeutic system (GITS) is used to treat angina and hypertension. The authors aimed to study the early intervention impact on arterial stiffness and pulse wave velocity (PWV) independent of its blood-pressure-(BP) lowering effect in mild hypertensive patients. Methods This single-center, single-arm, open-label, prospective, Phase IV study recruited patients with mild hypertension and increased PWV from December 2013 to December 2014 (N=138; age, 18–75 years; systolic blood pressure, 140–160 mmHg; diastolic BP, 90–100 mmHg; increased brachial–ankle pulse wave velocity [baPWV, ≥12 m/s]). Nifedipine GITS (30 mg/d) was administered for 24 weeks to achieve target BP of <140/90 mmHg. The dose was uptitrated at 60 mg/d in case of unsatisfactory BP reduction after 4 weeks. Primary study end point was the change in baPWV after nifedipine GITS treatment. Hemodynamic parameters (office BP, 24-hour ambulatory BP monitoring, and heart rate and adverse events) were evaluated at baseline and followed-up at 2, 4, 8, 12, 18, and 24 weeks. Results Majority of patients (n=117; 84.8%) completed the study. baPWV decreased significantly at 4 weeks compared with baseline (1,598.87±239.82 vs 1,500.89±241.15 cm/s, P<0.001), was stable at 12 weeks (1,482.24±215.14 cm/s, P<0.001), and remained steady through 24 weeks (1,472.58±205.01 cm/s, P<0.001). Office BP reduced from baseline to week 4 (154/95 vs 136/85 mmHg) and remained steady until 24 weeks. Nifedipine GITS significantly decreased 24-hour ambulatory BP monitoring (P<0.001) after 24 weeks from baseline. Mean arterial pressure and pulse pressure were lowered significantly after 4, 12, and 24 weeks of treatment (P<0.001). These changes in baPWV were significantly correlated with changes in systolic blood pressure, diastolic BP, and mean arterial pressure (P<0.05), but not with changes in pulse pressure (P>0.05). There were no other drug-related serious adverse events. Conclusion Nifedipine GITS was considerably effective in reducing baPWV and BP, indicating improvement in arterial stiffness as early as 4 weeks.

Treatment of right ventricular perforation during percutaneous coronary intervention : case report

Abstract Percutaneous coronary intervention (PCI) is widely used to treat stenotic coronary arteries caused by coronary heart disease. Coronary artery perforation is a rare but dreaded complication of PCI. Here, we report the successful treatment of a patient with coronary perforation of the right ventricular cavity. To our knowledge, this is the first report of its kind. The patient was a 69-year-old woman with intermittent chest tightness and chest pain of about five years’ duration who was hospitalised for severe chest tightness and pain persisting for three days. She had a history of hypertension and hyperlipidaemia; routine admission examination showed no other abnormalities. Results of routine blood, urine and stool tests, liver and kidney function, clotting time, electrocardiogram, chest radiography and echocardiography were normal. Although coil embolisation rather than balloon is safe and effective for treating coronary artery perforation, it may be not the best choice overall. If the perforation breaks through into the right ventricle, we may just monitor closely rather than treat. That course may be beneficial for patients in that it reduces the risk of myocardial cell necrosis. This case provides useful information for the treatment of such patients in the future.

APOLIPOPROTEIN E SUPPRESSES IL-12 PRODUCTION IN MACROPHAGES

Objectives Accumulation of T cells and macrophages in atherosclerotic plaques and the formation of antibodies directed against plaque proteins suggests that adaptive immunity contributes to the development of atherosclerosis. Apolipoprotein E (apoE) exerts potent anti-inflammatory effects that may contribute to protection against atherosclerosis independent of its role in lipid metabolism. Here, we investigated the expression of pro-inflammatory cytokine interleukin-12 (IL-12) in macrophages of apoE−/− mice and then further explored the molecular mechanisms. Methods In this study, peritoneal macrophages and bone marrow- derived macrophages elicited from wild-type (WT) or apoE knockout (apoE−/−) mice were stimulated with low-dose lipopolysaccharide (LPS), interferon-r (IFN-r) or LPS plus IFN-r for 24 h, followed by collection of culture supernatants for measurement of IL-12 p40 and p70 protein secretion by ELISA. Meanwhile, cells treated with these stimuli for 4 h were used for RNA isolation and IL-12 p35 and p40 mRNA detection by quantitative real-time PCR. Then, we transiently co-transfected a human IL-12 p35 promoter luciferase construct with different amounts of apoE expression vector or PTYB2 vector into THP-1 cells (a human macrophage cell line) by electroporation, followed by measurement of luciferase activity in cell lysates. Results The expression of IL-12 were upregulated to a significantly greater extent in apoE-deficient mice than in WT mice at both the mRNA and protein levels following administration of LPS or LPS plus IFN-r. ApoE suppressed IL-12 p35 promoter in a dose-dependent manner, indicating that apoE-mediated p35 gene suppression is regulated at the level of transcription. Moreover, cells co-transfected with the p35 promoter and the apoE-expressing vector showed decreased promoter activities in response to IFN-r and LPS treatments compared with cells co-transfected with the empty vector, PTYB2, further demonstrating that apoE suppressed IL-12 p35 gene transcription under both basal and inducible conditions. Conclusions Our study reveals that apoE suppresses IL-12 production at the level of transcription in macrophages, this effect may represent a novel anti-inflammatory activity of apoE.