Association of Uric Acid and C-reactive Protein with the Severity of Coronary Artery Disease Using SYNTAX Score and Clinical SYNTAX Score.

BACKGROUND: The SYNTAX score (SXscore), an anatomical-based scoring tool reflecting the complexity of coronary anatomy, has been associated with the mortality and prognosis of coronary artery disease (CAD). Clinical SYNTAX score (CSS), incorporating clinical factors further augmented the utility of the SXscore to longer-term risk. C-reactive protein (CRP) is related to SXscore. Serum uric acid (UA) is associated with atherosclerosis and CAD. However, serum uric acid combined with CRP may better predict the SXscore and CSS. METHODS: A total of 208 patients (mean age 57.82 ± 9.39 years) with chest pain were included in this study. All selected subjects underwent coronary artery angiography and blood test. The relationship between serum UA, CRP and SXscore, and CSS were analyzed. RESULTS: Age and CRP had a positive correlation with SXs and CSS. DM and fasting glucose correlated with SXscore and CSS respectively. In multivariate regression, serum UA, age, fasting glucose, and body mass index (BMI) were significant discriminant factors of high CSS. The predictive accuracy of CRP for SXscore >0 and high CSS using receiver operator characteristic curves was set at the cut off point of 0.205 mg/dL and 0.145 mg/dL respectively, (sensitivity 70.9% and 98%, specialty 48% and 23.2%). CONCLUSION: Serum CRP is correlated with SXscore and CSS, serum UA is independently associated with CSS. CRP predicts high CSS at a lower level than it predicts SXscore. Thus, serum CRP combined with serum UA may be useful to predict SXscore and CSS.

Association between heme oxygenase 1 gene promoter polymorphisms and susceptibility to coronary artery disease: a HuGE review and meta-analysis.

We performed a systematic review and meta-analysis of heme oxygenase 1 gene (HO-1) promoter polymorphisms and susceptibility to coronary artery disease (CAD) based on eligible studies retrieved from electronic databases from 2002 to 2013. Eleven studies, involving 10,170 patients with CAD and 6,868 controls, were included. Overall, no significantly decreased risk of CAD was found in persons with the SS genotype of the HO-1 (GT)n repeat length polymorphism compared with those with the LL + SL genotype. However, decreased risks of CAD were observed in the Asian subgroup, the coronary-artery-narrowing ≥50% subgroup, the myocardial infarction subgroup, the age- and sex-matched subgroup, and the good-quality-reports subgroup. The primary heterogeneity in the studies came from age and sex matching and the extent of coronary stenosis. CAD risk was significantly decreased for persons with the AA genotype of the T(-413)A single-nucleotide polymorphism versus those with the TT genotype, but most of the studies showed that the allele distribution was inconsistent with Hardy-Weinberg equilibrium. In this meta-analysis, we found that the (GT)n SS genotype was associated with decreased risk of CAD after controlling for biases due to age and sex matching, extent of coronary stenosis, ethnicity, and study quality. The relationship between the T(-413)A single-nucleotide polymorphism and CAD should be interpreted more cautiously.

MiR-132 inhibits expression of SIRT1 and induces pro-inflammatory processes of vascular endothelial inflammation through blockade of the SREBP-1c metabolic pathway.

PURPOSE: Inflammation participates centrally in all stages of atherosclerosis (AS), which begins with pro-inflammatory processes and inflammatory changes in the endothelium, related to lipid metabolism. MicroRNA (miRNA) inhibition of inflammation related to SIRT1 has been shown to be a promising therapeutic approach for AS. However, the mechanism of action is unknown. METHODS: We investigated whether miRNAs regulate the SIRT1 and its downstream SREBP-lipogenesis-cholesterogenesis metabolic pathway in human umbilical vein endothelial cells (HUVECs). HUVECs were transfected with miR-132 mimics and inhibitors, and then treated with or without tumor necrosis factor α (TNFα). The effects of miR-132 on pro-inflammatory processes, proliferation and apoptosis were assessed. RESULTS: We identified that the relative 3' UTR luciferase activities of SIRT1 were significantly decreased in miR-132 transfected HUVECs (0.338 ± 0.036) compared to control (P = 0.000). miR-132 inhibited SIRT1 expression of mRNA level in HUVECs (0.53 ± 0.06) (P < 0.01) as well as proteins of SIRT1. mRNA expression and protein levels of SREBP (0.45 ± 0.07), fatty acid synthase (FASN) (0.55 ± 0.09) and 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) (0.62 ± 0.08) (P < 0.01), which are downstream regulated genes, were reduced in HUVECs by miR-132. MiR-132 promoted pro-inflammatory processes and apoptosis of HUVECs induced by TNF-α, and inhibited its proliferation, viability and migration. CONCLUSIONS: SIRT1 mRNAs are direct targets of miR-132. miR-132 controls lipogenesis and cholesterogenesis in HUVECs by inhibiting SIRT1 and SREBP-1c expression and their downstream regulated genes, including FASN and HMGCR. Inhibition of SIRT1 by miR-132 was associated with lipid metabolism-dependent pro-inflammatory processes in HUVECs. The newly identified miRNA, miR-132 represents a novel targeting mechanism for AS therapy.

Correlation between comprehensive evaluation of coronary artery lesion severity and long-term clinical outcomes in Chinese octogenarians with acute coronary syndrome.

BACKGROUND: There is little known about long-term outcome data regarding acute coronary syndrome (ACS) in Chinese octogenarians (> 80 years old). Long-term outcomes of octogenarians with ACS may be associated with increased complicated coronary artery lesion severity. METHODS: We classified 536 consecutive octogenarians with ACS into four groups based on Gensini score. Survival and major adverse cardiac event (MACE) rates were calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify mortality predictors. The follow-up period was 27 (IQR15-36) months. RESULTS: The overall long-term mortality rate was 9.1% and increased from 3.0% in group 1 to 16.7% in group 4. Increasing coronary artery lesion severity was associated with increased long-term mortality and MACE rates. ROC curve analysis showed that the predictive cut-off value of Gensini score for mortality was 53. Gensini score provided significant reclassification of mortality (net reclassification index 0.195, P<0.01). Age, gender, heart rate, SBP, chronic renal failure, e-GFR, GRACE score, Gensini score, and ACS type were different between surviving and deceased patients. Notably, chronic renal failure (OR=2.55, P=0.036), GRACE score (OR=1.10, P=0.006), and Gensini score(OR=1.11, P=0.003) were the independent predictors of long-term mortality. CONCLUSIONS: Long-term mortality of octogenarians with ACS was associated with increased comprehensive coronary artery lesion severity. Gensini score was an effective parameter for evaluation of long-term mortality.

Long-term prognostic impact of cystatin C on acute coronary syndrome octogenarians with diabetes mellitus.

OBJECTIVE: Cystatin C (Cys C) is a marker of renal dysfunction. Prior studies have shown that blood Cys C is related to the prognosis of coronary heart disease. The aim of the present study was to evaluate the long-term prognostic impact of Cys C on acute coronary syndrome (ACS) octogenarians with diabetes mellitus (DM). METHODS: We enrolled 660 consecutive ACS octogenarians who underwent coronary angiography and were classified into two groups based on diabetes. The baseline characters and Cys C level were measured on admission. Survival curve was calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify predictors of mortality and of major adverse cardiac events (MACE) rate. RESULTS: There were 223 and 398 patients in groups DM and non-DM who fulfilled the follow-up. The average follow-up period was 28 (IQR 16-38) months. Diastolic blood pressure (DBP) was lower, ratios of hypertension and chronic renal failure (CRF), fasting blood glucose, HbA1c and Cys C levels were higher in DM group than those in non-DM group (P<0.01). The cumulative survival of DM group was significantly lower than that of non-DM group in the long term (P = 0.018). All cause mortality and MACE of DM group were higher than those of non-DM group (P<0.05). The plasma Cys C concentration (OR = 3.32, 95% CI = 1.18-10.92, P = 0.023) was the uniqueness independent predictor for long-term all cause mortality. The plasma Cys C concentration (OR = 2.47, 95% CI = 1.07-7.86, P = 0.029) and Genesis score (OR = 1.01, 95% CI = 1.00-1.03, P = 0.043) were independent predictors for MACE in DM group. ROC curve analysis showed that the predictive cut-off value of Cys C for mortality of DM group was 1.605 (0.718, 0.704). CONCLUSIONS: Cys C is an independent predictor for long-term mortality and MACE of ACS octogenarians with DM.

Evaluation of long-term follow-up with neointimal coverage and stent apposition after sirolimus-eluting stent implantation by optical coherence tomography.

BACKGROUND: Late stent thrombosis related to delayed endothelialization is a major concern after drug-eluting stent (DES) implantation. The long-term vascular response towards DES implantation remains unclear. Optical coherence tomography (OCT) is a high-resolution imaging modality which provides new opportunities for evaluating neointimal coverage and stent strut apposition after stent implantation. METHODS: Fifty two patients who accepted 64 sirolimus-eluting stents (SESs, Cypher Select) were enrolled in the study. The OCT procedure was performed in 20 patients at 12 months (group 1), 17 patients at 24 months (group 2), and 15 patients at 48 months (group 3) after SESs implantation, respectively. The neointimal hyperplasia (NIH) thickness and stent strut apposition were assessed at 1-mm interval, and the presence of thrombus was observed in each stent. RESULTS: The NIH thickness was significantly higher at 48 months than that of 12 months (0.1694 ± 0.1455 mm in G3 vs. 0.1455 ± 0.1373 mm in G1, P < 0.01) and 24 months (0.1514 ± 0.1296 mm in G2, P <0.01) after SESs implantation, but no significant difference existed between that of 12 months and 24 months (P > 0.05). Longer follow-up time was associated with significant decrease in the prevalence of uncovered struts (17.3% in group 1 vs. 8.8% in group 2 vs. 2.6% in group 3, P < 0.01) and malapposed struts (14.2% in group 1 vs. 10.3% in group 2 vs. 4.7% in group 3, P < 0.01). The incidence of intracoronary thrombus steadily decreased from 3.6% at 12 months to 2.4% at 24 months, and to 0.8% at 48 months (P < 0.01). CONCLUSION: Neointimal growth continued for as long as 48 months after SES implantation. NIH thickness increased insignificantly from 12 to 24 months, but markedly increased at 48 months after stent implantation. Late neointimal growth was accompanied by a higher rate of covered struts and lower rate of malapposed stent struts.

Correlation between major adverse cardiac events and coronary plaque characteristics.

BACKGROUND: Unstable plaque is believed to be responsible for major adverse cardiac events (MACE). OBJECTIVE: To determine whether coronary computed tomography angiography (CCTA) could be used to predict future MACE. METHODS: Patients undergoing CCTA between January 2008 and February 2010 were consecutively enrolled in the study. The hospital database was screened for patients who later developed acute ST segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) or cardiac death. Plaque scores were calculated and analyzed using one-way ANOVA to examine the relationship between plaque scores and MACE. RESULTS: Of the 8557 patients who underwent CCTA, 1055 had hospital records available for follow-up. During follow-up, 25 patients experienced MACE including death (six patients), heart failure (two patients), STEMI (11 patients) and NSTEMI (six patients). The plaque scores were significantly increased in patients who later died, developed heart failure or experienced STEMI (P<0.05). Calcification, erosion and severe stenosis were responsible for the events (P<0.05). Mild and moderate lesions, positive remodelling, drug-eluting stent placement, occlusion and diffuse lesions were not predictive of MACE (P>0.05). CONCLUSION: Severe calcification, erosion and severe stenosis predict death, heart failure and STEMI.

[An initial study on the feasibility of diagnosing myocardial ischemia with CT first-pass myocardial perfusion imaging at rest].

OBJECTIVE: To assess the feasibility and accuracy of CT first-pass myocardial perfusion imaging (CT first-pass MPI) at rest for diagnosis of myocardial ischemia. Results of adenosine-induced myocardial perfusion scintigraphy (MPS) were used as gold standard. METHODS: Twenty-two patients with suspected or diagnosed coronary artery disease (CAD) were included and CT coronary angiography (CTCA) and MPS were performed within 2 weeks. CT first-pass MPI detected myocardial ischemia results through analyzing the raw date of CTCA were compared with MPS results. RESULTS: The sensibility, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of CT first-pass MPI at rest for detecting myocardial ischemia were 92% (12/13), 78% (7/9), 86% (12/14), 88% (7/8) and 86% (19/22), respectively. CONCLUSION: CT first-pass MPI at rest could detect myocardial ischemia with an accuracy similar to that of MPS.

[Effect of angiotensin II and aldosterone on the proliferation of cardiac fibroblasts in rats].

OBJECTIVE: To investigate the effect of angiotensin II (ang II), aldosterone (ald) and their receptor antagonists losartan (los) and spironolactone (spi) on the proliferation and collagen production of cardiac fibroblasts (CFs) in rats. METHODS: CFs were isolated from neonatal SD rats by collagenase II method and purified with differential attachment and detachment method. The 3 or 4 passages of the CFs were divided into the following groups: angiotensin II, angiotensin II+aldosterone, aldosterone, angiotensin II+losartan, and aldosterone+spironolactone. The cell viability of the CFs was assessed by Cell Counting Kit-8 (CCK-8) after the drug administration. The mRNA and protein expression levels of COL1A1, COL3A1, MMP1 and TIMP1 were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot respectively. RESULTS: Ang II and Ald facilitated the proliferation rate of the CFs independently compared with that in the control group (38.5% vs 28.5%; P<0.05), and the proliferation rate in the ang II+ald group was higher than that in the ang II group and ald group alone (54.4%, P<0.05). Los and spi inhibited the effect induced by ang II and ald respectively (P<0.05). Compared with the control group, ang II and ald significantly enhanced COL1A1, COL3A1 and MMP1 expression both at the mRNA and protein levels (P<0.05), but the TIMP1 expression was inhibited (P<0.05), which could be abolished by corresponding receptor antagonists los and spi (P<0.05). CONCLUSION: Ang II and ald can promote the proliferation of CFs, and the COL1A1 and COL3A1 expression is enhanced both at mRNA and protein levels. Ang II and ald have synergistic effect when they are used together, while los and spi may restrain the effect. The mechanism is probably linked with the balance of MMPs/TIMPs.

[Ex vivo assessment of coronary lesions by optical coherence tomography and intravascular ultrasound in comparison with histology results].

OBJECTIVE: To explore the diagnostic accuracy of optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in the detection of ex vivo coronary plaques with different compositions compared with histology results. METHODS: OCT and IVUS were performed in 15 autopsied heart specimens and the isolated coronary artery was assessed by routine histological processing thereafter. Coronary plaques were classified into 3 types (lipid-rich plaque, calcified plaque and fibrous plaque) according to standard criteria respectively. Sensitivity and specificity for detection of different types of plaque by OCT and IVUS were calculated according histology results. RESULTS: Seventy seven coronary plaques were analyzed. OCT demonstrated a sensitivity and specificity of 69% and 88% for lipid-rich plaque, 93% and 92% for calcified plaque, 88% and 98% for fibrous plaque. IVUS demonstrated a sensitivity and specificity of 61% and 92%, 98% and 97%, 68% and 90% respectively. The agreement between OCT and IVUS in assessment of coronary plaque was 0.831 (Kappa = 0.72, P < 0.01). CONCLUSIONS: Both OCT and IVUS correctly detected ex vivo coronary plaques and there was a good agreement in assessment of coronary plaques between OCT and IVUS. OCT is superior to IVUS in assessment of fibrous plaque and is similar as IVUS in assessment of calcified plaque.

Incidence, predictors, and clinical impact of tissue prolapse after coronary intervention: an intravascular optical coherence tomography study.

OBJECTIVES: To evaluate the predictors of tissue prolapse after stenting and whether this phenomenon can affect the clinical outcome. METHODS: All consecutive patients who underwent optical coherence tomography (OCT) examination after stent implantation were included. Qualitative and quantitative assessment of tissue prolapse after stent implantation was performed. The lesions were classified into 4 groups according to the severity of tissue prolapse. We analyzed the clinical, procedural, and image-based predictors of severe tissue prolapse and evaluated the clinical impact of tissue prolapse. RESULTS: Tissue prolapse within the stented segment was visible in 102/104 (98.08%) cases. The frequency and severity of tissue prolapse was similar in acute coronary syndrome (ACS) and non-ACS lesions. The OCT-defined thin cap fibroatheroma (TCFA) was related with severe tissue prolapse (≥ grade III) (r = 17.722, p < 0.001). No difference in events was observed among different tissue prolapse groups during the hospitalization period and 1-year follow-up. CONCLUSIONS: The incidence of tissue prolapse after stent implantation was relatively high, irrespective of the clinical presentation. OCT-defined TCFA lesions were more likely with severe tissue prolapse (≥ grade III). Tissue prolapse was not associated with clinical events during the hospitalization period and 1-year clinical follow-up.

The combination of 64 multislice CT angiography and optical coherence tomography optimally characterizes coronary plaques.

OBJECTIVE: The European Society of Cardiology designated 2008 as the year of imaging. However, despite the intense focus on the many types of imaging and the relative benefits of each one, the optimal modalityfor the diagnosis of coronary artery disease remains controversial. Among the currently available techniques, coronary angiography (CA) is the most widely used. In light of the many recent improvements in imaging, a comparison of the different modalities for CAD diagnosis and treatment evaluation is urgently needed. MATERIAL AND METHODS: of the 1583 patients examined by computed tomography CA (CTCA) in the past 2 years, 28 with unstable angina also underwent CA and optical coherence tomography (OCT) evaluation. The coronary artery indices obtained with the three modalities were compared in this subset of patients. RESULTS: Minimal lumen diameter and reference lumen diameter were calculated independently based on the data obtained from each modality. The diameters measured by CTCA were significantly larger than those measured by CA or OCT (p < 0.05). Minimal cross-section area calculation was feasible only from the CTCA and OCT data, but not from the CA data. Again, the cross-sectional area measured by CTCA was significantly larger than that measured by OCT. Plaque diameter, remodelling index, plaque volume, and CT value could be measured only by CTCA. Disease extent was measured by CTCA using the method of J.K. Min and by CA using the Syntax Score. Intimal thickness and the thickness of the thrombus and fibrous cap could be evaluated only by OCT. CONCLUSION: A comparison of the three different imaging modalities (CA, CTCA, and OCT) in CAD pointed out the benefits as well as the limits. A combination of CA, CTCA, and OCT was found to provide the best approach to evaluating the coronary arteries. CTCA best revealed the vessel wall while OCT provided optimal visualization of the intima. The extent of coronary artery disease was best detered with CA and CTCA.

Correlation between acute coronary syndrome classification and multi-detector CT characterization of plaque.

OBJECTIVE: To determine if multi-detector CT (MDCT) characterization of plaque is correlated with the classification of acute coronary syndrome (ACS). METHODS: Altogether 1900 patients were examined by MDCT from December 2007 to May 2009, of whom 95 patients fulfilled the criteria of ACS. Those patients were divided into the discrete plaque group ( n=61) and diffuse plaque group ( n=34) based on the findings in MDCT. The clinical diagnosis of ACS and CT results were analyzed, including segment stenosis score, segment involvement score, 3-vessel plaque score, left main score, calcification score, and remodeling index. The incidences of major adverse cardiac events in follow-up period were also recorded. RESULTS: The patients of the diffuse plaque group were older than those of the discrete plaque group ( Pü0.0001). The diffuse plaque group presented more cases of hypertension, peripheral artery disease, diabetes, and heart failure than discrete plaque group (all P<0.05). All the 5 patients with ST-segment elevation myocardial infarction were found in discrete plaque group. The segment stenosis score of the discrete plaque group was lower than that of the diffuse plaque group(5.15±3.55 vs. 14.91±5.37, Pü0.001). The other four scores demonstrated significant inter-group difference as well (all P<0.05). The remodeling index of thediscrete plaque group was higher (1.12±0.16 vs.0.97±0.20, Pü0.05). Follow-up data showed that major adverse cardiac events occurred more frequently in diffuse plaque group than in discrete group (29.41% vs. 11.48%, P=0.0288). CONCLUSIONS: Characteristics of discrete and diffuse plaques may be significantly different among different classes of ACS. The diffuse plaque may present higher risk, correlated to higher mortality. The diagnosis of discrete and diffuse plaques by MDCT would provide a new insight into the prognosis and treatment of ACS.

[Value of combined CT coronary angiography and adenosine stress myocardial perfusion scintigraphy for diagnosis of coronary artery disease].

OBJECTIVE: To assess the accuracy and feasibility of combination of CT coronary angiography (CTCA) and adenosine stress myocardial perfusion scintigraphy (MPS) for diagnosis of coronary artery disease (CAD). METHODS: CTCA, MPS were performed in 105 patients with suspected or diagnosed CAD within 4 weeks before coronary angiography (CAG) examination. RESULTS: The sensibility, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 97.1%, 75.0%, 88.2%, 93.1% and 89.5%, respectively, for CTCA; 79.7%, 63.9%, 80.9%, 62.2% and 74.3%, respectively, for MPS and 97.2%, 98.5%, 98.5%, 89.7% and 95.2%, respectively, for CTCA + MPS. CONCLUSION: Combination of CTCA and adenosine stress MPS, which provided both anatomical and functional information of coronary vessels, could significantly increase the specificity and PPV of diagnosing CAD with CTCA.

[Changes of vasoactive substances in myocardium of chronic renal ischemia rats].

OBJECTIVE: To investigate the relationship between the vasoactive substances including endothelin-1 (ET-1), calcitonin gene-related peptide (CGRP), and nitric oxide (NO) in myocardium and the cardiac functions in chronic renal ischemia rats. METHODS: Male Wistar rats weighting 180-200 g were randomly divided into 2 groups: operation group (n=30) and sham operation group (n=10). A ligation of abdominal aorta between right and left renal artery was made by silk suture in operation group and the necrosis degree of aorta was about 50%. Aorta was not ligated in sham operation group. Sixteen weeks after operation, invasive measurement of blood pressure and cardiac function were performed, and content of ET-1, CGRP, and NO in myocardium were determined. RESULTS: Compared with sham operation group, blood pressure significantly increased in the operation group after ligation, along with decreased cardiac systolic and diastolic function, increased left ventricular mass index. After 16 weeks, compared with sham operation group, the content of ET-1 in cardiac tissue were significantly elevated in operation group [(361.0+/-118.7) vs. (503.4+/-139.6 ) pg/ml, P<0.01), along with significantly decreased CGRP content [(74.4+/-24.8) vs. (45.4+/-15.1) pg/ml, P<0.01). The content of ET-1 in cardiac tissue was negatively correlated with the maximum pressure rise rate of left ventricular r=-0.37, P<0.05). CONCLUSIONS: Chronic kidney ischemia caused by abdominal aorta ligation may result in the increase of ET-1 content in cardiac tissue and decrease of CGRP decreased. The content of ET-1 in cardiac tissue is also negatively correlated with left ventricular systolic function.

[Relationship between computed tomography coronary angiography and adenosine stress myocardial perfusion imaging for the assessment of coronary artery disease].

OBJECTIVE: To compare the accuracy of computed tomography coronary angiography (CTCA) and adenosine stress myocardial perfusion imaging in the diagnosis of coronary artery disease (CAD) and discuss their relationship. METHODS: Fifty-six patients, suspected or diagnosed as CAD, were performed with CTCA, MPI and coronary angiography (CAG) within 3 weeks. They were divided into 3 groups: no CAD, no obstructive CAD (coronary artery stenosis < 70%) and obstructive CAD (coronary artery stenosis > or = 70%). RESULTS: 5 patients were diagnosed as no CAD. 19 patients were diagnosed as no obstructive CAD and 32 patients were diagnosed as obstructive CAD by CTCA. While adenosine stress MPI suggested 26 patients normal, 18 patients had IPD and 29 patients had RPD. The sensibility, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CTCA were 100%, 55.6%, 92.2% and 100% versus 78.6%, 71.4%, 73.3% and 76.9% respectively for adenosine stress MPI. CONCLUSION: CTCA and adenosine stress MPI provide different and complementary information on CAD, anatomical versus functional. As compared with CAG, CTCA has a high accuracy of detecting CAD.

[Differences between adipose-derived stem cells and mesenchymal stem cells in differentiation into cardiomyocytes].

Adipose-derived stem cells (ASCs) are similar to bone marrow mesenchymal stem cells (MSCs) in growth kinetics, antigen expression and multi-lineage differentiation capacity. The present study was designed to investigate the differences between ASCs and MSCs in in vitro culture and differentiation into cardiomyocytes. ASCs were isolated from the fat tissue of New Zealand white rabbits while MSCs were obtained from rat bone marrow. Both ASCs and MSCs were cultured in Iscove's modified Dulbecco's medium supplemented with 15% fetal bovine serum in the same incubator and treated with various concentrations of 5-azacytidine. A clonogenic assay was used to quantify ASCs in fat tissue and MSCs in bone marrow. The number of ASCs in the fat tissue was much higher than that of MSCs in the bone marrow quantified by clonogenic assay, and MSCs showed a remarkably slower proliferative rate compared with ASCs, especially at primary passage. ASCs began to attach to the bottom of the culture flask 12 h after seeding. The cells in culture assumed a short spindle shape under a phase-contrast microscope and did not form clusters. The phenotype was maintained through repeated subcultures under nonstimulating conditions. No other cell phenotype was observed. MSCs attached to the culture flask at 24-48 h after seeding and grew in clusters. The cells were fibroblast-like and prone to senescence or differentiation into adipose cells. Both ASCs and MSCs before treatment with 5-azacytidine were stained positively for CD29, CD44 and CD105 but negatively for CD34 and CD45, α-sarcromeric actin, cardiac troponin T and von Willebrand factor. ASCs differentiated into cardiomyocytes only after treatment with 6-9 µmol/L of 5-azacytidine, while MSCs differentiated into cardiomyocytes with 3-15 µmol/L of 5-azacytidine. After treatment with ideal dose of 5-azacytidine, ASCs began to change their morphology and showed multinucleation within the first week and formed a ball-like appearance thereafter, while MSCs showed multinucleation at the second week and formed a stick-like appearance at 3-4 weeks. The percentage of ASCs differentiated into cardiomyocytes after treatment with 5-azacytidine was significantly higher than that of MSCs. The age of animal had no significant influence on the tissue content, proliferation and differentiation rate of ASCs. However, the tissue content of MSCs in bone marrow decreased with increased age of animal and MSCs from old donor rats exhibited less myogenic cells than those from the young rats after exposure to 5-azacytidine. These results indicate that ASCs have advantages over MSCs in tissue content, homology, growth and differentiation rate, suggesting that ASCs are more suitable for cellular cardiomyoplasty than MSCs.

The clinical application value of the plasma copeptin level in the assessment of heart failure with reduced left ventricular ejection fraction: A cross-sectional study.

This study aimed to evaluate the clinical applicability of the plasma copeptin level to assess heart failure with reduced left ventricular ejection fraction (HFrEF).One hundred thirty-one patients with HFrEF, 127 patients with heart failure with preserved left ventricular ejection fraction (HFpEF), and 119 healthy candidates were involved. The basic data and examination results of patients were collected. The heart function of the patients with HFrEF and HFpEF were graded on the basis of the criteria of New York Heart Association (NYHA) classification. The plasma copeptin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were tested using enzyme-linked immunosorbent assays (ELISAs).The copeptin and NT-proBNP levels were higher in the HFrEF group than in the HFpEF group. The copeptin and NT-proBNP values increased as the NYHA grade increased in the patients with HFrEF. However, for the patients with HFpEF, the copeptin levels did not change markedly as the NYHA grade increased. The copeptin levels were positively correlated with the NT-proBNP levels in the patients with HFrEF; however, there was no correlation between the copeptin and NT-proBNP values in the patients with HFpEF.Copeptin is involved in the process of progression in patients with HFrEF and the copeptin values might be useful for HFrEF prediction and assessment in the clinic.

Transplantation of autologous adipose-derived stem cells ameliorates cardiac function in rabbits with myocardial infarction.

BACKGROUND: Adipose-derived stem cells (ADSCs) are capable of differentiating into cardiomyogenic and endothelial cells in vitro. We tested the hypothesis that transplantation of ADSCs into myocardial scar may regenerate infracted myocardium and restore cardiac function. METHODS: ADSCs were isolated from the fatty tissue of New Zealand white rabbits and cultured in Iscoves modified dulbeccos medium. Three weeks after ligation of left anterior descending coronary artery of rabbits, either a graft of untreated ADSCs (UASCs, n = 14), 5-azacytidine-pretreated ADSCs (AASCs, n = 13), or phosphate buffer saline (n = 13) were injected into the infarct region. Transmural scar size, cardiac function, and immunohistochemistry were performed 5 weeks after cell transplantation. RESULTS: ADSCs in culture demonstrated a fibroblast-like appearance and expressed CD29, CD44 and CD105. Five weeks after cell transplantation, transmural scar size in AASC-implanted hearts was smaller than that of the other hearts. Many ADSCs were differentiated into cardiomyocytes. The AASCs in the prescar appeared more myotube-like. AASCs in the middle of the scar and UASCs, in contrast, were poorly differentiated. Some ADSCs were differentiated into endothelial cells and participate in vessel-like structures formation. All the ADSC-implanted hearts had a greater capillary density in the infarct region than did the control hearts. Statistical analyses revealed significant improvement in left ventricular ejection fraction, myocardial performance index, end-diastolic pressure, and peak +dP/dt, in two groups of ADSC-implanted hearts relative to the control hearts. AASC-implanted hearts had higher peak -dP/dt values than did control, higher ejection fraction and peak +dP/dt values than did UASC-implanted hearts. CONCLUSIONS: ADSCs transplanted into the myocardial scar tissue formed cardiac islands and vessel-like structures, induced angiogenesis and improved cardiac function. 5-Azacytidine pretreatment before implantation is desirable for augmenting myogenesis. Transplantation of 5-azacytidine-treated ADSCs into the myocardial scar was more efficient than that of untreated ADSCs in preservation of cardiac function.