scholarly journals Cardiac markers in five different breeds of rabbits (Oryctolagus cuniculus Linnaeus, 1758) used for cardiovascular research

2016 ◽  
Vol 36 (8) ◽  
pp. 737-742 ◽  
Author(s):  
Felipp S. Ferreira ◽  
Flávia L. Barretto ◽  
Arianne Fabres ◽  
Leonardo S. Silveira ◽  
Claudio B. Carvalho
Keyword(s):  
Normal Values ◽  
Heart Diseases ◽  
Large Population ◽  
Reference Interval ◽  
Cardiac Biomarkers ◽  
Cardiac Markers ◽  
Physiological Variable ◽  
Cardiovascular Research ◽  
Tukey Test ◽  
Commercial Kits

Abstract: Cardiac biomarkers for clinical and experimental heart diseases have previously been evaluated in rabbits. However, several laboratory assays performed and reported with inconsistent results. This study aimed to assess the effects of breed on serum ANP, CRP, and ACE and establish reference interval (RI) for these biomarkers in a large population of healthy rabbits. Ninety-seven adult rabbits from five breeds were included in this study. Assays were performed using specific ELISA commercial kits. The results were statistically analyzed using ANOVA, Tukey test (p<0.05), arithmetic mean, RI of mean, and standard deviation. A significant effect of breed was shown, indicating different RI between breeds for each biomarker. In conclusion, this study demonstrated that breed is an important physiological variable influencing the normal values of cardiac markers in healthy rabbits.

Regenerating Damaged Myocardium: A Review of Stem-Cell Therapies for Heart Failure

2021 ◽  
Author(s):  
Dihan Fan ◽  
Hanrong Wu ◽  
Huashan Peng ◽  
Kaichao Pan ◽  
Rongxue Wu
Keyword(s):  
Drug Testing ◽  
Cardiac Myocyte ◽  
Cardiac Fibroblasts ◽  
Heart Diseases ◽  
Contributing Factors ◽  
Myocardial Repair ◽  
Cardiovascular Research ◽  
Cell Therapies ◽  
Induced Pluripotent ◽  
Promising Source

Cardiovascular disease (CVD) is one of the contributing factors to more than one-third of human mortality and the leading cause of death worldwide. Cardiac myocyte death is a fundamental process in cardiac pathologies caused by various heart diseases, including myocardial infarction. Thus, strategies for replacing fibrotic tissue in the infarcted region with functional myocardium have long been a goal of cardiovascular research. This review focuses primarily on induced-pluripotent stem cells (iPSCs), which have emerged as perhaps the most promising source of cardiomyocytes for both therapeutic applications and drug testing. We also briefly summarize other stems- and progenitor-cell populations that have been used for regenerative myocardial therapy and attempt to generate cardiomyocytes directly from cardiac fibroblasts (i.e., transdifferentiation), which, if successful, may enable the pool of endogenous cardiac fibroblasts to be used as an in-situ source of cardiomyocytes for myocardial repair.

scholarly journals Regenerating Damaged Myocardium: A Review of Stem-Cell Therapies for Heart Failure

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3125
Author(s):  
Dihan Fan ◽  
Hanrong Wu ◽  
Kaichao Pan ◽  
Huashan Peng ◽  
Rongxue Wu
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Myocyte ◽  
Cardiac Fibroblasts ◽  
Heart Diseases ◽  
Contributing Factors ◽  
Myocardial Repair ◽  
Cardiovascular Research ◽  
Cell Therapies ◽  
Promising Source

Cardiovascular disease (CVD) is one of the contributing factors to more than one-third of human mortality and the leading cause of death worldwide. The death of cardiac myocyte is a fundamental pathological process in cardiac pathologies caused by various heart diseases, including myocardial infarction. Thus, strategies for replacing fibrotic tissue in the infarcted region with functional myocardium have long been a goal of cardiovascular research. This review begins by briefly discussing a variety of somatic stem- and progenitor-cell populations that were frequently studied in early investigations of regenerative myocardial therapy and then focuses primarily on pluripotent stem cells (PSCs), especially induced-pluripotent stem cells (iPSCs), which have emerged as perhaps the most promising source of cardiomyocytes for both therapeutic applications and drug testing. We also describe attempts to generate cardiomyocytes directly from cardiac fibroblasts (i.e., transdifferentiation), which, if successful, may enable the pool of endogenous cardiac fibroblasts to be used as an in-situ source of cardiomyocytes for myocardial repair.

scholarly journals Advanced Technologies to Target Cardiac Cell Fate Plasticity for Heart Regeneration

2021 ◽  
Vol 22 (17) ◽  
pp. 9517
Author(s):  
Gianluca Testa ◽  
Giorgia Di Benedetto ◽  
Fabiana Passaro
Keyword(s):  
Cell Fate ◽  
Disease Modeling ◽  
Heart Diseases ◽  
Cellular Reprogramming ◽  
Cardiac Cell ◽  
New Paradigm ◽  
Cardiovascular Research ◽  
Injured Myocardium

The adult human heart can only adapt to heart diseases by starting a myocardial remodeling process to compensate for the loss of functional cardiomyocytes, which ultimately develop into heart failure. In recent decades, the evolution of new strategies to regenerate the injured myocardium based on cellular reprogramming represents a revolutionary new paradigm for cardiac repair by targeting some key signaling molecules governing cardiac cell fate plasticity. While the indirect reprogramming routes require an in vitro engineered 3D tissue to be transplanted in vivo, the direct cardiac reprogramming would allow the administration of reprogramming factors directly in situ, thus holding great potential as in vivo treatment for clinical applications. In this framework, cellular reprogramming in partnership with nanotechnologies and bioengineering will offer new perspectives in the field of cardiovascular research for disease modeling, drug screening, and tissue engineering applications. In this review, we will summarize the recent progress in developing innovative therapeutic strategies based on manipulating cardiac cell fate plasticity in combination with bioengineering and nanotechnology-based approaches for targeting the failing heart.

Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures

Blood ◽  
2009 ◽  
Vol 114 (3) ◽  
pp. 723-732 ◽  
Author(s):  
Marianna Prokopi ◽  
Giordano Pula ◽  
Ursula Mayr ◽  
Cécile Devue ◽  
Joy Gallagher ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mononuclear Cells ◽  
Lectin Binding ◽  
Large Population ◽  
Protein Composition ◽  
Population Based ◽  
Endothelial Progenitor ◽  
Cardiovascular Research ◽  
Proteomic Approach ◽  
Cellular Phenotypes

Abstract The concept of endothelial progenitor cells (EPCs) has attracted considerable interest in cardiovascular research, but despite a decade of research there are still no specific markers for EPCs and results from clinical trials remain controversial. Using liquid chromatography–tandem mass spectrometry, we analyzed the protein composition of microparticles (MPs) originating from the cell surface of EPC cultures. Our data revealed that the conventional methods for isolating mononuclear cells lead to a contamination with platelet proteins. Notably, platelets readily disintegrate into platelet MPs. These platelet MPs are taken up by the mononuclear cell population, which acquires “endothelial” characteristics (CD31, von Willebrand factor [VWF], lectin-binding), and angiogenic properties. In a large population-based study (n = 526), platelets emerged as a positive predictor for the number of colony-forming units and early outgrowth EPCs. Our study provides the first evidence that the cell type consistent with current definitions of an EPC phenotype may arise from an uptake of platelet MPs by mononuclear cells resulting in a gross misinterpretation of their cellular progeny. These findings demonstrate the advantage of using an unbiased proteomic approach to assess cellular phenotypes and advise caution in attributing the benefits in clinical trials using unselected bone marrow mononuclear cells (BMCs) to stem cell-mediated repair.

P5387CRISPR/dCas9 Activated Expression of Cardiomyocyte Differentiation Factors in CDCs in Myocardial Infarctions

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Sano ◽  
S Ishigami ◽  
S Bandaru ◽  
T Ito ◽  
S Sano
Keyword(s):  
Transcriptional Activation ◽  
Heart Diseases ◽  
Large Population ◽  
Treatment Strategies ◽  
Neonatal Rat ◽  
Cardiomyocyte Differentiation ◽  
Differentiation Potential ◽  
Regulatory Regions ◽  
Specific Differentiation ◽  
Differentiation Factors

Abstract Background Existing therapies against myocardial infarction (MI) involve disease management by preventing additional damage to the heart muscle. However, new treatment strategies are in greater demand, which deems to focus on restoring cardiac function by replacing the damaged cells after MI, rather than merely manage the disease. Cardiosphere-derived cells (CDCs) have emerged as a potential source of cardiac regenerative therapy. In spite of being a promising option, the poor differentiation potential of CDCs to develop into a functional population of cardiomyocytes has always been a significant setback. Purpose The purpose of the present study centers to overcome the aforementioned setback by enhancing the efficiency of rat CDCs to develop into a large population of cardiomyocytes by intrinsic activation of cardio-specific differentiation factors (TNNT2, GATA4, Mef2c) by Crispr/dcas9 assisted transcriptional enhancement system. Methods In the foremost step, an exhaustive screening was performed to identify the specific sequences in endogenous regulatory regions (enhancers and promoters) responsible for transcriptional activation of the TNNT2 gene. Once, potential regulatory regions at proximal and distal end of TNNT2 were identified, crRNAs were designed complementing these regions for recruiting Crispr/dcas9 system fused with transcriptional activator like VP64 (CRISPR-dCas9-VP64). Two distinct plasmids were constructed with crRNA (RFP fused) inserts and CRISPR-dCas9-VP64 (GFP fused) followed by transfection in CDCs those isolated from the heart of a neonatal rat. Post transfection, CDCs were then analyzed for the quantitative expression of cardiomyocyte differentiation factors as well as for fibroblast differentiation factors in comparison with un-transfected CDCs. Results We identified a panel of specific crRNA targeting the enhancers and promoters which demonstrated significantly higher expression of differentiation factors like troponin, GATA4, and Mef2c. Further, the fluorescent visualization with GFP and RFP was prominent in the CDCs confirming that these panel of crRNA enhanced the expression of differentiation factors compared to the un-transfected counterparts. Interestingly, the same panel crRNA, in contrast, demonstrated diminished expression of fibroblast differentiation factors like Col1A1, clearly emphasizing that the CRISPR dCas9 system recruitment at regulatory regions forms an efficient molecular targeting system for enhancing the differentiation potential of CDCs into cardiomyocytes. Conclusion We have identified endogenous regulatory regions responsible for an intrinsic activation of cardio-specific differentiation factors assisted by Crispr/dcas9 gene transcriptional system. We anticipate the method developed herein can enhance and cardiomyogenic efficiency of CDCs to differentiate into a large population of cardiomyocytes to treat Ischemic heart diseases.

scholarly journals Epidemiology of Heart Disease of Uncertain Etiology: A Population Study and Review of the Problem

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 687 ◽  
Author(s):  
Alessandro Menotti ◽  
Paolo Emilio Puddu
Keyword(s):  
Risk Factors ◽  
Heart Disease ◽  
Population Study ◽  
Serum Cholesterol ◽  
Heart Diseases ◽  
Large Population ◽  
Hdl Cholesterol ◽  
Cox Proportional Hazards ◽  
Italian Population ◽  
Uncertain Etiology

Background and objectives: Previous epidemiological studies have identified a group of heart diseases (here called heart diseases of uncertain etiology—HDUE) whose characteristics were rather different from cases classified as coronary heart disease (CHD), but frequently confused with them. This analysis had the purpose of adding further evidence on this issue based on a large population study. Materials and Methods: Forty-five Italian population samples for a total of 25,272 men and 21,895 women, free from cardiovascular diseases, were examined with measurement of some risk factors. During follow-up, CHD deaths were those manifested as myocardial infarction, other acute ischemic attacks, and sudden death of probable coronary origin, after reasonable exclusion of other causes. Cases of HDUE were those manifested only as heart failure, chronic arrhythmia, and blocks in the absence of typical coronary syndromes. Cox proportional hazards models were computed separately for CHD and HDUE, with 11 risk factors as possible predictors. Results: During an average of 7.4 years (extremes 1–16) there were 223 CHD and 150 HDUE fatal events. Male sex, age, smoking habits, systolic blood pressure, serum cholesterol, and plasma glucose were significantly and directly related to CHD events, while high density lipoprotein (HDL) cholesterol was so in an inverse way. The same risk factors were predictive of HDUE events except serum cholesterol and HDL cholesterol. Multivariable hazards ratio of serum cholesterol (delta = 1 mmol/L) was higher in the CHD model (1.24, 95% CI 1.11–1.39) than in the HDUE model (1.03, 0.5% C.I. 0.89–1.19) and the difference between the respective coefficients was statistically significant (p = 0.0444). Age at death was not different between the two end-points. Conclusions: CHD and HDUE are probably two different morbid conditions, only the first one is likely bound to gross atherosclerotic lesions of coronary arteries and linked to blood lipid levels. We reviewed the problem in epidemiological investigations and addressed inflammation as a potential cofactor to differentiate between CHD and HDUE.

scholarly journals Choice of Statistical Tools for Outlier Removal Causes Substantial Changes in Analyte Reference Intervals in Healthy Populations

2020 ◽  
Vol 66 (12) ◽  
pp. 1558-1561 ◽  
Author(s):  
Peter E Hickman ◽  
Gus Koerbin ◽  
Julia M Potter ◽  
Nicholas Glasgow ◽  
Juleen A Cavanaugh ◽  
...  
Keyword(s):  
Statistical Methods ◽  
Population Studies ◽  
Large Population ◽  
Large Body ◽  
Reference Interval ◽  
Reference Intervals ◽  
Outlier Removal ◽  
Reference Limit ◽  
Statistical Measures ◽  
Upper Reference Limit

Abstract Background Reference intervals are an important aid in medical practice as they provide clinicians a guide as to whether a patient is healthy or diseased. Outlier results in population studies are removed by any of a variety of statistical measures. We have compared several methods of outlier removal and applied them to a large body of analytes from a large population of healthy persons. Methods We used the outlier exclusion criteria of Reed-Dixon and Tukey and calculated reference intervals using nonparametric and Harrell-Davis statistical methods and applied them to a total of 36 different analytes. Results Nine of 36 analytes had a greater than 20% difference in the upper reference limit, and for some the difference was 100% or more. Conclusions For some analytes, great importance is attached to the reference interval. We have shown that different statistical methods for outlier removal can cause large changes to reported reference intervals. So that population studies can be readily compared, common statistical methods should be used for outlier removal.

scholarly journals Biosensor for determination of glucose in real samples of beverages

2012 ◽  
Vol 32 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Flavio Marques Lopes ◽  
Karla de Aleluia Batista ◽  
Gustavo Luiz Aleluia Batista ◽  
Kátia Flávia Fernandes
Keyword(s):  
Orange Juice ◽  
Sodium Phosphate ◽  
Operational Parameters ◽  
Real Samples ◽  
Glucose Determination ◽  
Tukey Test ◽  
Sodium Phosphate Buffer ◽  
Commercial Kits ◽  
Operational Range

A biosensor was developed for spectrophotometric determination of glucose concentrations in real samples of orange juice energetic drinks, and sport drinks. The biosensor consisted of glucose oxidase (GOD) and horseradish peroxidase (HRP) immobilized onto polyaniline activated with glutaraldehyde (PANIG). Immobilization parameters were optimized for GOD, and maximum immobilization yield was 16% when 5.0 mg of PANIG and 8.9 U prepared in 0.1 mol.L-1 sodium phosphate buffer (pH 7.0) reacted for 60 minutes at 4 °C with gentle stirring. The linear operational range for glucose determination using optimized operational parameters was between 0.05 and 6.0 mg.mL-1 with a very good reproducibility of response. The results obtained in the biosensor were compared with those obtained using free enzymes (commercial kits) and then validated through statistical analysis using the Tukey test (95% confidence interval).

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