Prenatal Exposure to LPS Alters The Intrarenal RAS in Offspring, Which Is Ameliorated by Adipose Tissue-Derived Mesenchymal Stem Cells.

BACKGROUND: Prenatal lipopolysaccharide (LPS) exposure causes hypertension in rat offspring through an unknown mechanism. Here, we investigated the role of the intrarenal renin-angiotensin system (RAS) in hypertension induced by prenatal LPS exposure and also explored whether adipose tissue-derived mesenchymal stem cells (ADSCs) can ameliorate the effects of prenatal LPS exposure in rat offspring. METHODS: Sixty-four pregnant rats were randomly divided into 4 groups (n = 16 in each), namely, a control group and an LPS group, which were intraperitoneally injected with vehicle and 0.79 mg/kg LPS, respectively, on the 8th, 10th, and 12th days of gestation; an ADSCs group, which was intravenously injected with 1.8 × 107 ADSCs on the 8th, 10th, and 12th days of gestation; and an LPS + ADSCs group, which received a combination of the treatments administered to the LPS and ADSCs groups. RESULTS: Prenatal LPS exposure increased blood pressure, Ang II expression, Ang II-positive, monocyte and lymphocyte, apoptotic cells in the kidney, and induced renal histological changes in offspring; however, the LPS and control groups did not differ significantly with respect to plasma renin activity levels, Ang II levels, or renal function. ADSCs treatment attenuated the blood pressure and also ameliorated the other effects of LPS-treated adult offspring. CONCLUSIONS: Prenatal exposure to LPS activates the intrarenal RAS but not the circulating RAS and thus induces increases in blood pressure in adult offspring; however, ADSCs treatment attenuates the blood pressure increases resulting from LPS exposure and also ameliorates the other phenotypic changes induced by LPS treatment by inhibiting intrarenal RAS activation.

Assessment of mitochondrial DNA mutations in Chinese family with essential hypertension.

Mitochondrial DNA (MtDNA) mutations played an important role in the development of essential hypertension. Mitochondrial tRNA point mutations, caused the failure in tRNA metabolism, responsible for the pathogenesis of this complex disease. In this study, we evaluated the possible role of the 4329C >G mutation in the clinical expression of hypertension in a Chinese family. Analysis of the complete mtDNA sequence variants showed that other mutations may play synergic roles in the phenotypic manifestation of hypertension. In addition, other potential pitfalls were also discussed in this context.

Prognostic value of total bilirubin in patients with angina pectoris undergoing percutaneous coronary intervention.

BACKGROUND: Bilirubin is a potent antioxidant and previous studies have reported the relationship between low serum bilirubin concentration and atherosclerosis. OBJECTIVE: To evaluate the prognostic value of serum total bilirubin (STB) in patients with angina pectoris undergoing percutaneous coronary intervention (PCI). METHODS: In total of 1419 patients (931 men, mean age 60.9±10.5 years) with angina pectoris who had undergone successfully percutaneous coronary intervention (PCI) were included in this study. Patients were divided into 2 groups according to the median baseline STB (0.49 mg/dL in this cohort), which was measured before the PCI. Patients with a STB ≥0.49 mg/dL were classified into the high STB group and those with a STB <0.49 mg/dL were classified into the low STB group. RESULTS: The incidence of in-hospital mortality and myocardial infraction was similar in the two groups. After a mean follow-up of 29.0±7.6 months, the incidence of death/myocardial infarction/stroke was significantly higher in low STB group compared with high STB group. Multivariate Cox regression analysis showed that low STB was an independent predictor of death/myocardial infarction/stroke (hazard ratio (HR) = 1.59, 95% confidence interval (CI) = 1.04-2.41, P = 0.031). The cumulative survival rate free from death/myocardial infarction/stroke was lower in low STB group than in high STB group (P = 0.002). CONCLUSION: Low STB levels before PCI is an independent predictor of long-term adverse clinical outcomes in patients with angina pectoris.

Serum total bilirubin and long-term outcome in patients undergoing percutaneous coronary intervention.

PURPOSE: The purpose of this study was to investigate the associated between serum total bilirubin (STB) levels and long-term outcomes in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). METHODS: A total of 1,273 consecutive patients were enrolled. Patients were grouped according to their baseline STB levels: Group 1 (STB < 3.4 µmol/L), Group 2 (3.4 µmol/L ≤ STB ≤ 10.3 µmol/L), Group 3 (10.3 µmol/L < STB ≤ 17.1 µmol/L), and Group 4 (STB < 17.1 µmol/L) and the rate of major adverse cardiovascular events (MACE) was determined RESULTS: A total of 1,152 patients were successfully followed up (90.5%) for a mean period of 30 ± 5 months, including 187 patients experiencing a major adverse cardiovascular event (MACE: death from any cause, myocardial infarction, repeat revascularization or readmission). The MACE rate in Groups 3 and 4 was lower than in Groups 1 and 2 (P < 0.01). After adjusted the confounding factors with Cox regression analysis, the MACE rates in Groups 2-4 were still lower than in Group 1 (Group 2, RR=0.293, 95% CI 0.167-0.517, P < 0.01; Group 3, RR=0.142, 95% CI 0.065-0.312, P < 0.01; Group 4, RR=0.134, 95% CI 0.071-0.252, P < 0.01). The cumulative survival rates of Groups 3 and 4 were higher than that of Groups 1and 2 (P < 0.01). CONCLUSIONS: High STB concentration is associated with lower MACE in patients with ACS after PCI.

Domestic versus imported drug-eluting stents for the treatment of patients with acute coronary syndrome.

BACKGROUND: The application of coronary stents, especially drug-eluting stents (DESs), has made percutaneous coronary intervention (PCI) one of important therapeutic methods for CHD. DES has reduced the in-stent restenosis to 5%-9% and significantly improved the long-term prognosis of patients with CHD. The study aimed to investigate the long-term efficacy and safety of domestic drug-eluting stents (DESs) in patients with acute coronary syndrome (ACS). METHODS: All patients with ACS who had undergone successful percutaneous coronary intervention (PCI) in the First Affiliated Hospital of Zhengzhou University from July 2009 to December 2010 were included in this study. Patients were excluded from the study if they were implanted with bare metal stents or different stents (domestic and imported DESs) simultaneously. The included patients were divided into two groups according to different stents implanted: domestic DESs and imported DESs. RESULTS: In the 1 683 patients of this study, 1 558 (92.6%) patients were followed up successfully for an average of (29.1±5.9) months. 130 (8.3%) patients had major adverse cardiovascular events (MACEs), including cardiac death in 32 (2.1%) patients, recurrent myocardial infarction in 16 (1%), and revascularization in 94 (6%). The rates of cardiac death, recurrent myocardial infarction, revascularization, in-stent restenosis, stent thrombosis and other MACEs were not significantly different between the two groups (all P>0.05). Multivarite logistic regression revealed that diabetes mellitus (OR=1.75, 95%CI: 1.09-2.82, P=0.021), vascular numbers of PCI (OR=2.16, 95%CI: 1.22-3.83, P=0.09) and PCI with left main lesion (OR=9.47, 95%CI: 2.96-30.26, P=0.01) were independent prognostic factors of MACEs. The Kaplan-Meier method revealed that there was no significant difference in cumulative survival rates and survival rates free from clinical events between the two groups (all P>0.05). CONCLUSIONS: The incidences of clinical events and cumulative survival rates are not statistically different between domestic DESs and imported DESs. Domestic DES is effective and safe in the treatment of patients with ACS.

Long-term follow-up results in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents: results from a single high-volume PCI centre.

OBJECTIVE: To assess both short-term and long-term prognosis in consecutive patients with coronary heart disease treated with drug-eluting stents in a high-volume percutaneous coronary intervention (PCI) centre. DESIGN: Observational cohort study. SETTING: A hospital in the Henan province, China, between 2009 and 2011. PARTICIPANTS: A total of 2533 patients were enrolled. Patients with ST-elevation myocardial infarction (STEMI) treated with urgent PCI accounted for 3.9% of cases; patients with STEMI treated with delayed PCI accounted for 20.5% of cases; patients with stable angina accounted for 16.5% of cases; and patients with non-ST elevation acute coronary syndrome (NSTE-ACS) accounted for 58.6% of cases. PRIMARY OUTCOMES: Death, major adverse cardiac and cerebrovascular events (MACCE: death/myocardial infarction/stroke), and target vessel revascularisation. RESULTS: Follow-up after a median of 29.8 months was obtained for 2533 patients (92.6%). The mortality rate during hospitalisation was highest in the urgent PCI group (p<0.001). During follow-up, although the incidences of death and MACCE were highest in the urgent PCI group, no significant differences were observed among the different groups. The incidences of cardiac death and myocardial infarction were significantly higher in the paclitaxel-eluting stent (PES) group than in the sirolimus-eluting stent (SES) group. Independent predictors of death during follow-up were age, left ventricular ejection function <40%, diabetes mellitus, prior coronary artery bypass graft and chronic total occlusion. CONCLUSIONS: PCI patients with STEMI had the worst hospital and long-term prognosis. The mortality rate after hospital increased markedly in patients with NSTE-ACS. SESs seem to be more effective than PESs.

Red blood cell distribution width and long-term outcome in patients undergoing percutaneous coronary intervention in the drug-eluting stenting era: a two-year cohort study.

BACKGROUND: Previous studies suggest the higher the red blood cell distribution width (RDW) the greater the risk of mortality in patients with coronary artery disease (CAD). However, the relationship between RDW and long-term outcome in CAD patients undergoing percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) remains unclear. This study was designed to evaluate the long-term effect of RDW in patients treated with drug-eluting stent for CAD. METHODS: In total of 2169 non-anemic patients (1468 men, mean age 60.2 ± 10.9 years) with CAD who had undergone successful PCI and had at least one drug-eluting stent were included in this study. Patients were grouped according to their baseline RDW: Quartile 1 (RDW<12.27%), Quartile 2 (12.27% ≤ RDW <13%), Quartile 3 (13% ≤ RDW<13.5%), and Quartile 4 (RDW ≥ 13.5). RESULTS: The incidence of in-hospital mortality and death or myocardial infarction was significantly higher in Quartiles 3 and 4 compared with Quartile 1 (P<0.05). After a follow-up of 29 months, the incidence of all-cause death and stent thrombosis in Quartile 4 was higher than in Quartiles 1, 2, and 3 (P<0.05). The incidence of death/myocardial infarction/stroke and cardiac death in Quartile 4 was higher than in Quartiles 1 and 2 (P<0.05). Multivariate Cox regression analysis showed that RDW was an independent predictor of all-cause death (hazard ratio (HR) = 1.37, 95% confidence interval (CI) = 1.15-1.62, P<0.001) and outcomes of death/myocardial infarction/stroke (HR = 1.21, 95% CI = 1.04-1.39, P = 0.013). The cumulative survival rate of Quartile 4 was lower than that of Quartiles 1, 2, and 3 (P<0.05). CONCLUSION: High RDW is an independent predictor of long-term adverse clinical outcomes in non-anemic patients with CAD treated with DES.

Plaque characteristics and serum pregnancy-associated plasma protein A levels predict the no-reflow phenomenon after percutaneous coronary intervention.

OBJECTIVES: To investigate the relationship between serum plasma pregnancy-associated plasma protein A (PAPP-A) and coronary plaque characteristics, and their prognostic value for coronary no-reflow after percutaneous coronary intervention (PCI). METHODS: Patients with unstable angina undergoing PCI were divided into a normal reflow group and a no-reflow group after stent deployment. Coronary blood flow was measured angiographically; plaque components were detected by virtual histology intravascular ultrasound. Serum PAPP-A and high-sensitivity C-reactive protein (hsCRP) were measured before PCI. Cardiac troponin T (cTnT) was measured before and 24 h after PCI. RESULTS: A total of 166 patients with unstable angina undergoing PCI were included: normal reflow group (n = 145) and no-reflow group (n = 21), after stent deployment. Baseline coronary blood flow was similar in the two groups. The no-reflow group had plaques with less-fibrotic tissue and a larger necrotic core, more thin-cap fibroatheromas and plaque ruptures, and higher serum PAPP-A, hsCRP and post-PCI cTnT levels than the normal reflow group. Serum PAPP-A was correlated negatively with plaque fibrotic area and positively with necrotic core area. CONCLUSION: High serum PAPP-A and plaque lesions with a large necrotic core are associated with the no-reflow phenomenon after PCI, in patients with unstable angina.

The predictive value of plasma cystatin C for acute coronary syndrome treated with percutaneous coronary intervention.

BACKGROUND: This study was designed to evaluate the value of plasma cystatin C in predicting adverse cardiac events after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). METHODS: A total of 605 patients (404 male, mean age 60.4 ± 10.6 years) with ACS underwent successful PCI. Patients were divided into 4 groups according to the level of cystatin C, which was measured before the PCI: Q1 (<1.02 mg/L), Q2 (1.02-1.16 mg/L), Q3 (1.17-1.34 mg/L), and Q4 (≥1.35 mg/L). RESULTS: After a follow-up of 14.3 ± 1.7 months, the incidence of mortality, nonfatal myocardial infarction, and target lesion revascularization in the Q2, Q3, and Q4 groups was higher than in the Q1 group (P < .001). The incidence of heart failure in the Q3 and Q4 groups was higher than in the Q1 group (P < .05). Multivariate Cox regression analysis showed that cystatin C elevation was an independent predictor of major adverse cardiac events. The cumulative survival rate of the Q3 and Q4 groups was lower than in the Q1 group (P < .001). CONCLUSION: High plasma cystatin C concentration is an independent predictor of major adverse cardiac events in patients with ACS treated with PCI.

[Simvastatin inhibits hypertension-induced cardiac hypertrophy in rats through activation of heme oxygenase-1/carbon monoxide pathway].

To investigate the anti-cardiac hypertrophic mechanism of statins, thirty-eight male Wistar rats were randomly allocated to four groups. Rats in model group received nitric oxide synthase inhibitor, N-nitro-L-arginine (L-NNA) 15 mg/(kg.d) by peritoneal injection. Rats in simvastatin treatment groups were given simultaneously L-NNA as those in model group and simvastatin 5 or 30 mg/(kg.d) intragastrically respectively. Rats in control group received the same volume of normal sodium. Left ventricular function, left ventricular mass index (LVMI), the content of brain natriuretic peptide (BNP) in plasma and myocardium, myocardial hydroxyproline and heme oxygenase activity were determined after 6 weeks. The results showed that rats in model group developed significant cardiac hypertrophy associated with reduced left ventricular function compared with the control group. However, compared with the model group, L-NNA-induced cardiac hypertrophy of rats was significantly relieved in simvastatin treatment groups, associated with improved left ventricular function, decreased LVMI, lower BNP levels in plasma and myocardium, lower content of myocardial hydroxyproline, and increased myocardial heme oxygenase (HO) activity. In cultured rat neonatal cardiomyocytes, simvastatin (30 or 100 mumol/L) significantly increased heme oxygenase-1 (HO-1) mRNA expression, HO activity as well as the production of CO in cardiomyocytes. Cultured with zinc protoporphyrin, a HO inhibitor, or simvastatin alone did not change [(3)H]leucine uptake of cardiomyocytes. However, cocultured with simvastatin significantly inhibited the cardiomyocyte [(3)H]leucine uptake induced by angiotensin II in a concentration-dependent manner. Cotreatment with zinc protoporphyrin significantly abolished the suppressive effect of simvastatin on cardiomyocyte [(3)H]leucine uptake. These data suggest that the activation of HO-1/CO pathway may be one of the important mechanisms by which statins inhibit cardiac hypertrophy caused by hypertension.