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Rationale: Myocardial vulnerability to ischemia/reperfusion (I/R) injury is strictly regulated by energy substrate metabolism. Branched chain amino acids (BCAA), consisting of valine, leucine and isoleucine, are a group of essential amino acids that are highly oxidized in the heart. Elevated levels of BCAA have been implicated in the development of cardiovascular diseases; however, the role of BCAA in I/R process is not fully understood. The present study aims to determine how BCAA influence myocardial energy substrate metabolism and to further clarify the pathophysiological significance during cardiac I/R injury. Methods: Parameters of glucose and fatty acid metabolism were measured by seahorse metabolic flux analyzer in adult mouse cardiac myocytes with or without BCAA incubation. Chronic accumulation of BCAA was induced in mice receiving oral BCAA administration. A genetic mouse model with defective BCAA catabolism was also utilized. Mice were subjected to MI/R and the injury was assessed extensively at the whole-heart, cardiomyocyte, and molecular levels. Results: We confirmed that chronic accumulation of BCAA enhanced glycolysis and fatty acid oxidation (FAO) but suppressed glucose oxidation in adult mouse ventricular cardiomyocytes. Oral gavage of BCAA enhanced FAO in cardiac tissues, exacerbated lipid peroxidation toxicity and worsened myocardial vulnerability to I/R injury. Etomoxir, a specific inhibitor of FAO, rescued the deleterious effects of BCAA on I/R injury. Mechanistically, valine, leucine and their corresponding branched chain α-keto acid (BCKA) derivatives, but not isoleucine and its BCKA derivative, transcriptionally upregulated peroxisome proliferation-activated receptor alpha (PPAR-α). BCAA/BCKA induced PPAR-α upregulation through the general control nonderepresible-2 (GCN2)/ activating transcription factor-6 (ATF6) pathway. Finally, in a genetic mouse model with BCAA catabolic defects, chronic accumulation of BCAA increased FAO in myocardial tissues and sensitized the heart to I/R injury, which could be reversed by adenovirus-mediated PPAR-α silencing. Conclusions: We identify BCAA as an important nutrition regulator of myocardial fatty acid metabolism through transcriptional upregulation of PPAR-α. Chronic accumulation of BCAA, caused by either dietary or genetic factors, renders the heart vulnerable to I/R injury via exacerbating lipid peroxidation toxicity. These data support the notion that BCAA lowering methods might be potentially effective cardioprotective strategies, especially among patients with diseases characterized by elevated levels of BCAA, such as obesity and diabetes.

Background Contrast-induced nephropathy (CIN) is one of major and serious complications in patients undergoing percutaneous coronary intervention (PCI). It is unknown whether increased urinary adiponectin (UAPN), a sensitive marker for early renal function impairment, is associated with an increased risk of CIN. Therefore, we prospectively investigate the association of UAPN with CIN. Methods We prospectively enrolled 208 patients who were undergoing elective PCI. The baseline UAPN was assessed prior to PCI. The ROC analysis was used to evaluate the predictive value of UAPN for CIN. Multivariate logistic regression analysis was performed to analyze the independent risk factors for CIN. Results Of 208 patients, CIN occurred in 19 patients (9.13%), and 6 of them (2.88%) required dialysis. Patients with CIN had a higher UAPN level than those without CIN (17.15 ± 12.36 vs. 10.29 ± 3.04 ng/ml, P 124 μmol/L (OR, 4.210; 95% CI, 1.297–13.669; P

Summary Aims: Angiotensin receptor blockers (ARBs) exert favorable effects on the vascular system, which are not directly related to hypertension lowering function. The no-reflow phenomenon determines the prognosis in patients after acute myocardial infarction (AMI). Early ARB treatment has many beneficial effects on the prognosis after AMI. In this study, we tested the hypothesis that ARB treatment before admission would have beneficial effects on the development of the no-reflow phenomenon after infarction. Methods: We investigated 276 consecutive patients with AMI undergoing successful primary percutaneous coronary intervention (PCI). No-reflow was defined as thrombolysis in myocardial infarction (TIMI) flow grade

Primary cultured rat aortic vascular smooth muscle cells (VSMCs) were exposed to different intensities of low-frequency electromagnetic fields (LFEMFs) at 20, 40, and 60 mT for different time periods (10, 20, and 30 minutes). Furthermore, osteopontin (OPN) mRNA and protein expressions were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Matrix metalloproteinase-2 (MMP-2) activity was measured using gelatin zymography. The results showed that the OPN mRNA and protein expressions and MMP-2 activity of VSMCs were inhibited by exposure to LFEMFs of different intensities in a dose-dependent manner (P < 0.05) but not in a time-dependent manner. In conclusion, exposure to LFEMFs of appropriate intensity for a suitable time period can result in the inhibition of the OPN expression and MMP-2 activity of VSMCs, indicating the potential prophylactic and therapeutic effects of LFEMFs on restenosis (RS) following percutaneous coronary intervention (PCI).

Different subsets of T lymphocytes have different functions in atherosclerosis advancement. T helper 1 cells and T regulatory 1 cells have been demonstrated to play opposite roles in rupture of atherosclerotic lesion. However, the role of novel subset of T regulatory cells, known as CD4+CD25+Foxp3+ T cells, remains largely unknown in coronary artery disease (CAD). In this study, we investigated the peripheral CD4+CD25+Foxp3+ T cells of patients with CAD and controls. The patients submitted were divided into three groups: stable angina pectoris (SA) group, unstable angina pectoris (UA) group and acute myocardial infarction (AMI) group. We analyzed the frequencies of peripheral CD4+CD25+Foxp3+ T cells and T helper 1/T helper 2 cells, expression of Foxp3 in CD4+CD25+ T subsets and cytokines pattern in patients and controls. We found that the reduction of CD4+CD25+Foxp3+ T lymphocytes was consistent with the expansion of Th1 cells in patients with unstable CAD. The reversed development between CD4+CD25+ Tregs and Th1 cells might contribute to plaque destabilization.

Angiotensin receptor blockers (ARBs) exert favorable effects on the vascular system, which are not directly related to hypertension lowering function. The no-reflow phenomenon determines the prognosis in patients after acute myocardial infarction (AMI). Early ARB treatment has many beneficial effects on the prognosis after AMI. In this study, we tested the hypothesis that ARB treatment before admission would have beneficial effects on the development of the no-reflow phenomenon after infarction.We investigated 276 consecutive patients with AMI undergoing successful primary percutaneous coronary intervention (PCI). No-reflow was defined as thrombolysis in myocardial infarction (TIMI) flow grade3, which was determined by the TIMI frame count method using angiographic images obtained just after PCI and stenting.Compared with patients without ARB treatment, patients with ARB had more frequently hypertension and ST resolution (P0.05), but no significant difference was found in the other clinical characteristics (age, sex, Hyperlipidaemia, Diabetes mellitus, etc) between the two groups. A total of 51 patients receiving chronic ARB treatment before admission have lower incidence of the no-reflow phenomenon than those without chronic ARB treatment (8.7% and 26.7%, P= 0.003). However, the incidence of the no-reflow phenomenon between the patients with and without hypertension had no significant difference. Multivariable logistic regression analysis revealed that ARB pretreatment was a significant predictor of the no-reflow phenomenon, whereas blood pressure was found to be insignificant.Chronic pretreatment of ARB is associated with the reduction of the no-reflow phenomenon in patients with reperfused AMI and could preserve microvascular integrity after AMI independent of blood pressure lowering, which may contribute to better functional recovery.

It is still not known whether the glial cell activation of locus coeruleus (LC) is involved in the neurophysiologic mechanism of the acute phase of heart disease. The aim of this study was to investigate whether the glial cell activation of LC responds to acute cardiac injury (ACI).In this study, ACI was established by intramyocardial injection of formalin. Afterward, we analysed c-Fos, OX42, GFAP and P2X(4)R expression levels in the LC of the rats by immunofluorescence staining or Western blot analysis.There was no significant difference in the levels of these markers in the LC between the normal control and the sham-operated groups. Following ACI, up-regulation of GFAP, OX42 and P2X(4)R expression levels were observed in locus coeruleus of the rats. The peak expression time was at hour 24. P2X(4)R was colocalized with OX42 in activated microglias, but not with GFAP in activated astrocytes. Compared with the control group, the ACI group showed a high expression level of c-Fos at hour 1 with a peak expression level at hour 2.The results showed that LC glia cells, like neurons, could sensitively respond to cardiovascular nociception induced by ACI at different time points. Results of this study may provide insights into the role of glial activation in response to ACI and may represent a potential strategy for investigation of neurophysiologic mechanism of cardiac pain.

To investigate the effects of constant magnetic field (CMF) on proliferation and migration of bone marrow-derived endothelial progenitor cells (EPCs) under rapamycin intervention.EPCs were isolated from rat bone marrow by density gradient centrifugation and cultured on fibronectin-coated dishes. Six days later the attached cells were divided into 5 groups: control group, rapamycin (1 ng/ml) group, and 3 rapamycin + CMF groups (treated with CMF of the doses 0.1 mT, 0.5 mT, and 1.0 mT respectively). Samples were collected 24 hours after incubation. Cell proliferation was measured by MTT chromatometre. EPC migration was detected with modified Boyden chamber assay.The EPC proliferation ability of the rapamycin group, expressed by absorbance, was (0.252 +/- 0.006), significantly lower than that of the control group [(0.328 +/- 0.025), P0.05]. The number of migrating EPC was (31 +/- 3) cells, significantly lower than that of the control group [(48 +/- 5), P0.05]. The EPC proliferation ability of the rapamycin + CMF 0.5 mT and 1.0 mT groups, expressed by absorbance, were (0.278 +/- 0.008) and (0.280 +/- 0.010) respectively, both significantly higher than that of the control group (both P0.05). The migrating EPC number of the rapamycin + CMF 0.5 mT and 1.0 mT groups were (37 +/- 3) and (38 +/- 4) respectively, both significantly higher than that of the control group (both P0.05).CMF of the doses of 0.5 mT and 1.0 mT antagonizes the effects of rapamycin on EPCs, increasing the proliferation and migration of EPCs.

Summary Aims: Angiotensin receptor blockers (ARBs) exert favorable effects on the vascular system, which are not directly related to hypertension lowering function. The no-reflow phenomenon determines the prognosis in patients after acute myocardial infarction (AMI). Early ARB treatment has many beneficial effects on the prognosis after AMI. In this study, we tested the hypothesis that ARB treatment before admission would have beneficial effects on the development of the no-reflow phenomenon after infarction. Methods: We investigated 276 consecutive patients with AMI undergoing successful primary percutaneous coronary intervention (PCI). No-reflow was defined as thrombolysis in myocardial infarction (TIMI) flow grade

Objectives To evaluate the initial and long-term clinical outcomes of patients with unprotected left main (ULM) stenosis undergoing percutaneous coronary intervention (PCI) with drug eluting stents (DES) at XiJing Hospital Centre in real world patient population. Methods After excluding acute ST-segment elevation myocardial infarction and bailout stenting, 798 patients treated for ULM disease with DES from January 2003 to December 2011 at XiJing Hospital were enrolled. The clinical outcomes of ULM treated with DES were evaluated by major adverse cardiac events (MACE) and stent thrombosis (ST) during in-hospital period and after long-term follow-up respectively. MACE was defined as cardiac death, non-fatal myocardial infarction (MI) and clinically driven target lesion revascularisation (TLR). ST was evaluated in accordance with the Academic Research Consortium (ARC) definitions. Results The mean age of study population was 62±10 years, 649 (81%) patients were male, 199 (25%) patients were diabetic, and the mean ejection fraction was 54%±11%. 71 (9%) patients had an ostial and 27 (3%) had a shaft lesion (nondistal subgroup), 700 (88%) patients had a bifurcation lesion (distal subgroup). In distal subgroup, 416 (59%) patients were treated with 1 stent (1-stent subgroup) and 284 (41%) were treated with 2 stent (2-stent subgroup). Among 2-stent subgroup, 74 (11%) patients were treated with crush (crush subgroup), 86 (12%) were treated with culotte (culotte subgroup), 43 (6%) were treated with kissing (kissing subgroup) and 81 (12%) were treated with T stenting (T subgroup). Angiographic and clinical successes of PCI were obtained in all patients. During the in-hospital period, MACE occurred in 7 (0.8%) patients including 5 (0.6%) cardiac deaths and 2 (0.2%) MIs. one patient had definite (died) and four patients had probable stent thrombosis (1 had a MI and 3 died). During the long-term follow-up duration of 27±20 months, MACE occurred in 176 (22%) patients including 25 (3%) cardiac deaths, 16 (2%) MIs and 135 (17%) TLRs. six patients had probable (died) and 12 patients had possible stent thrombosis (2 had MI and 10 died). There were no significant differences in in-hospital MACE rates between nondistal and distal subgroup, between 1-stent and 2-stent subgroup and among different 2-stent technique subgroups. After long-term follow-up, the TLR rate was significantly higher in distal subgroup than in nondistal subgroup (18% vs 9%, p Conclusions Treatment of ULM with DES is feasible and safe with good in-hospital and acceptable long-term clinical results. Compared with ostial and shaft lesion, distal bifurcation lesion is associated with a worse long-term TLR rate. 1-stent technique had a better long-term MACE rate than 2-stent technique when distal bifurcation lesion was treated, whereas different 2-stent techniques had similar clinical outcomes.