scholarly journals Cardiac telomere length in heart development, function, and disease

2017 ◽  
Vol 49 (7) ◽  
pp. 368-384 ◽  
Author(s):  
S. A. Booth ◽  
F. J. Charchar
Keyword(s):  
Heart Disease ◽  
Telomere Length ◽  
Heart Development ◽  
Heart Function ◽  
Cardiac Cells ◽  
Future Research ◽  
Proliferative Potential ◽  
Heart Cells ◽  
Telomere Attrition ◽  
Specific Regulation

Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury.

Characterization of a novel subset of cardiac cells and their progenitors in the Drosophila embryo

Development ◽  
2000 ◽  
Vol 127 (22) ◽  
pp. 4959-4969 ◽  
Author(s):  
E.J. Ward ◽  
J.B. Skeath
Keyword(s):  
Heart Development ◽  
Cell Types ◽  
Cardiac Cells ◽  
Lineage Tracing ◽  
Drosophila Embryo ◽  
Heart Cells ◽  
Pericardial Cells ◽  
Asymmetric Divisions ◽  
Genetic Mechanisms

The Drosophila heart is a simple organ composed of two major cell types: cardioblasts, which form the simple contractile tube of the heart, and pericardial cells, which flank the cardioblasts. A complete understanding of Drosophila heart development requires the identification of all cell types that comprise the heart and the elucidation of the cellular and genetic mechanisms that regulate the development of these cells. Here, we report the identification of a new population of heart cells: the Odd skipped-positive pericardial cells (Odd-pericardial cells). We have used descriptive, lineage tracing and genetic assays to clarify the cellular and genetic mechanisms that control the development of Odd-pericardial cells. Odd skipped marks a population of four pericardial cells per hemisegment that are distinct from previously identified heart cells. We demonstrate that within a hemisegment, Odd-pericardial cells develop from three heart progenitors and that these heart progenitors arise in multiple anteroposterior locations within the dorsal mesoderm. Two of these progenitors divide asymmetrically such that each produces a two-cell mixed-lineage clone of one Odd-pericardial cell and one cardioblast. The third progenitor divides symmetrically to produce two Odd-pericardial cells. All remaining cardioblasts in a hemisegment arise from two cardioblast progenitors each of which produces two cardioblasts. Furthermore, we demonstrate that numb and sanpodo mediate the asymmetric divisions of the two mixed-lineage heart progenitors noted above.

Confocal imaging of calcium in intact ventricular muscle provides a new view of excitation-contraction coupling

1996 ◽  
Vol 54 ◽  
pp. 738-739
Author(s):  
W.G. Wier
Keyword(s):  
Local Control ◽  
Cardiac Tissue ◽  
Cell Function ◽  
Isolated Heart ◽  
Cardiac Cells ◽  
Confocal Imaging ◽  
Ion Concentration ◽  
Heart Cell ◽  
Free Calcium ◽  
Heart Cells

A fundamentally new understanding of cardiac excitation-contraction (E-C) coupling is being developed from recent experimental work using confocal microscopy of single isolated heart cells. In particular, the transient change in intracellular free calcium ion concentration ([Ca2+]i transient) that activates muscle contraction is now viewed as resulting from the spatial and temporal summation of small (∼ 8 μm3), subcellular, stereotyped ‘local [Ca2+]i-transients' or, as they have been called, ‘calcium sparks'. This new understanding may be called ‘local control of E-C coupling'. The relevance to normal heart cell function of ‘local control, theory and the recent confocal data on spontaneous Ca2+ ‘sparks', and on electrically evoked local [Ca2+]i-transients has been unknown however, because the previous studies were all conducted on slack, internally perfused, single, enzymatically dissociated cardiac cells, at room temperature, usually with Cs+ replacing K+, and often in the presence of Ca2-channel blockers. The present work was undertaken to establish whether or not the concepts derived from these studies are in fact relevant to normal cardiac tissue under physiological conditions, by attempting to record local [Ca2+]i-transients, sparks (and Ca2+ waves) in intact, multi-cellular cardiac tissue.

scholarly journals Assessment of the Telomere Length and Its Effect on the Symptomatology of Parkinson’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 137
Author(s):  
Tina Levstek ◽  
Sara Redenšek ◽  
Maja Trošt ◽  
Vita Dolžan ◽  
Katarina Trebušak Podkrajšek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Telomere Length ◽  
Repetitive Sequences ◽  
Housekeeping Gene ◽  
Cellular Aging ◽  
Brain Diseases ◽  
Motor Complications ◽  
Telomere Attrition ◽  
Significant Difference

Telomeres, which are repetitive sequences that cap the end of the chromosomes, shorten with each cell division. Besides cellular aging, there are several other factors that influence telomere length (TL), in particular, oxidative stress and inflammation, which play an important role in the pathogenesis of neurodegenerative brain diseases including Parkinson’s disease (PD). So far, the majority of studies have not demonstrated a significant difference in TL between PD patients and healthy individuals. However, studies investigating the effect of TL on the symptomatology and disease progression of PD are scarce, and thus, warranted. We analyzed TL of peripheral blood cells in a sample of 204 PD patients without concomitant autoimmune diseases and analyzed its association with several PD related phenotypes. Monochrome multiplex quantitative PCR (mmqPCR) was used to determine relative TL given as a ratio of the amount of DNA between the telomere and albumin as the housekeeping gene. We found a significant difference in the relative TL between PD patients with and without dementia, where shorter TL presented higher risk for dementia (p = 0.024). However, the correlation was not significant after adjustment for clinical factors (p = 0.509). We found no correlations between TLs and the dose of dopaminergic therapy when the analysis was adjusted for genetic variability in inflammatory or oxidative factors. In addition, TL influenced time to onset of motor complications after levodopa treatment initiation (p = 0.0134), but the association did not remain significant after adjustment for age at inclusion and disease duration (p = 0.0781). Based on the results of our study we conclude that TL contributes to certain PD-related phenotypes, although it may not have a major role in directing the course of the disease. Nevertheless, this expends currently limited knowledge regarding the association of the telomere attrition and the disease severity or motor complications in Parkinson’s disease.

scholarly journals AB0308 NO SIGNS OF CONGESTIVE HEART DISEASE PROGRESSION IN PATIENTS WITH RHEUMATOID ARTHRITIS ON IL-6 RECEPTOR ANTAGONIST AFTER 12 MONTHS TREATMENT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1452.3-1453
Author(s):  
A. Martynova ◽  
T. Popkova ◽  
H. Gerasimova
Keyword(s):  
Rheumatoid Arthritis ◽  
Heart Disease ◽  
Receptor Antagonist ◽  
Disease Progression ◽  
European Heart Journal ◽  
Heart Function ◽  
Clinical Signs ◽  
Left Ventricular ◽  
Ultrasound Evaluation ◽  
Congestive Heart Disease

Background:N-terminal pro-brain natriuretic peptide (NT-proBNP) is a known marker of heart dysfunction, mainly described in patients with high activity of rheumatoid arthritis (RA). Further knowledge of the influence of the IL-6 receptor antagonist, tocilizumab (TCZ), on NT-proBNP levels and systolic heart function is yet to be obtained.Objectives:Access the effect of 12 months TCZ therapy on NT-proBNP levels, transthoracal ehocardiography results and analyze the association between congestive heart disease progression and RA activity.Methods:37 RA patients (pts) (31F/6M); median age 56,5 [48; 63,5] years; disease duration 48 [6; 348] months; DAS28 score 6,15 [5,44; 6,45]; rheumatoid factor (RF)+100%; anti–citrullinated protein antibody (ACPA) + 79,6% were treated in an open-label study with TCZ (8 mg/kg every 4 weeks). Identification of NT-pro-BNT in blood serum, transthoracal ultrasound evaluation of left ventriculum ejection fraction (LVEF), E/A ratio performed at baseline and 12 months.Results:11 (29,7%) pts had congestive heart disease (CHD) (II functional class of NYHA), 7 (18,9%) pts having signs of mild left ventricular dysfunction (LVD) as dyspnea, shortness of breath, cardiotropic treatment remained the same in the course of the study. After 12 month TCZ treatment as RA activity lowered (DAS28 2.32 [1,75; 3,15], р<0,05), NT-proBNP levels decreased (100,95 [57.9; 117.6] pg/ml to 90,46 [33.62; 106.6] pg/ml), along with elevation of LVEF (60,75 [60; 70]% to 67,68 [62.5; 73.5], p = 0,001). Increase of E/A (0,97 [0.8; 1.17] to 1,04 [0.7; 1.42] correlated with decrease of NT-proBNP level (r = -0,63, p=0,036). Raise of LVEF over 12 months correlated with decrease of RA activity according to SDAI scale (r= -0,670, p<0,05). No significant relationship between NT-proBNP levels, LVEF, E/A and other scales measuring RA activity was found. Clinically all patients had improvement in evaluation of their health and no signs of CHD or RVD progression were found.Conclusion:Use of TCZ in patients with active RA showed none to positive influence on heart condition, specifically, lowering NT-proBNP levels, improving LVEF and reducing clinical signs of LVD.References:[1]Pan Y, Li D, Ma J, Shan L, Wei M. NT-proBNP test with improved accuracy for the diagnosis of chronic heart failure. Medicine (Baltimore). 2017 Dec;96(51):e9181.[2]D Novikova, I Kirillova, E Markelova et al. The first report of significantly improvement of NT-proBNP level in rheumatoid arthritis patients treated with tofacitinib during 12-month follow-up, European Heart Journal, Volume 40, Issue Supplement_1, October 2019, ehz745.0836.[3]Pappas DA, Nyberg F, Kremer JM et al. Clin Rheumatol. 2018 Sep;37(9):2331-2340.Disclosure of Interests:None declared

Abstract 257: Clonal Analysis Of Multipotent Cardiovascular Progenitors That Generate Cardiomyocytes During Development

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Konstantina Ioanna Sereti ◽  
Paniz Kamran Rashani ◽  
Peng Zhao ◽  
Reza Ardehali
Keyword(s):  
Single Cell ◽  
Heart Development ◽  
Cardiac Development ◽  
Clonal Analysis ◽  
Cardiac Cells ◽  
Single Cell Level ◽  
Reporter System ◽  
Cell Level ◽  
Cardiac Progenitors

It has been proposed that cardiac development in lower vertebrates is driven by the proliferation of cardiomyocytes. Similarly, cycling myocytes have been suggested to direct cardiac regeneration in neonatal mice after injury. Although, the role of cardiomyocyte proliferation in cardiac tissue generation during development has been well documented, the extent of this contribution as well as the role of other cell types, such as progenitor cells, still remains controversial. Here we used a novel stochastic four-color Cre-dependent reporter system (Rainbow) that allows labeling at a single cell level and retrospective analysis of the progeny. Cardiac progenitors expressing Mesp1 or Nkx2.5 were shown to be a source of cardiomyocytes during embryonic development while the onset of αMHC expression marked the developmental stage where the capacity of cardiac cells to proliferate diminishes significantly. Through direct clonal analysis we provide strong evidence supporting that cardiac progenitors, as opposed to mature cardiomyocytes, are the main source of cardiomyocytes during cardiac development. Moreover, we have identified quadri-, tri-, bi, and uni-potent progenitors that at a single cell level can generate cardiomyocytes, fibroblasts, endothelial and smooth muscle cells. Although existing cardiomyocytes undergo limited proliferation, our data indicates that it is mainly the progenitors that contribute to heart development. Furthermore, we show that the limited proliferation capacity of cardiomyocytes observed during normal development was enhanced following neonatal cardiac injury allowing almost complete regeneration of the scared tissue. However, this ability was largely absent in adult injured hearts. Detailed characterization of dividing cardiomyocytes and proliferating progenitors would greatly benefit the development of novel therapeutic options for cardiovascular diseases.

scholarly journals Applications of miRNAs in cardiac development, disease progression and regeneration

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jeremy Kah Sheng Pang ◽  
Qian Hua Phua ◽  
Boon-Seng Soh
Keyword(s):  
Cardiac Development ◽  
Control Cell ◽  
Proliferative Potential ◽  
Heart Cells ◽  
Cardiovascular Development ◽  
Developmental Defects ◽  
Protein Coding ◽  
Cardiac Progenitors ◽  
Multiple Levels ◽  
Cell Niche

AbstractDevelopment of the complex human heart is tightly regulated at multiple levels, maintaining multipotency and proliferative state in the embryonic cardiovascular progenitors and thereafter suppressing progenitor characteristics to allow for terminal differentiation and maturation. Small regulatory microRNAs (miRNAs) are at the level of post-transcriptional gene suppressors, which enhance the degradation or decay of their target protein-coding mRNAs. These miRNAs are known to play roles in a large number of biological events, cardiovascular development being no exception. A number of critical cardiac-specific miRNAs have been identified, of which structural developmental defects have been linked to dysregulation of miRNAs in the proliferating cardiac stem cells. These miRNAs present in the stem cell niche are lost when the cardiac progenitors terminally differentiate, resulting in the postnatal mitotic arrest of the heart. Therapeutic applications of these miRNAs extend to the realm of heart failure, whereby the death of heart cells in the ageing heart cannot be replaced due to the arrest of cell division. By utilizing miRNA therapy to control cell cycling, the regenerative potential of matured myocardium can be restored. This review will address the various cardiac progenitor-related miRNAs that control the development and proliferative potential of the heart.

scholarly journals 5-bromo-2'-deoxyuridine-stimulated calcium ion- or magnesium ion-dependent ecto-(adenosine triphosphatase) activity of cultured hamster cardiac cells

1977 ◽  
Vol 164 (3) ◽  
pp. 645-652 ◽  
Author(s):  
G A Coetzee ◽  
W Gevers
Keyword(s):  
Adenosine Triphosphatase ◽  
Primary Cultures ◽  
Cardiac Cells ◽  
Cell Protein ◽  
Heart Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Active Centre ◽  
Cellular Dna ◽  
Hamster Heart

1. Treatment of hamster heart cells in primary culture with 5-bromo-2'-deoxyuridine resulted in the greatly increased activity of a particulate Ca2+- or Mg2+-dependent ATPase (adenosine triphosphatase). 2. 5-Bromo-2'-deoxyuridine exerted these effects only when it was incorporated into cellular DNA, and then in a concentration-dependent manner. 3. Serially replated cells contained less of the activity (expressed as a function of total cell protein) than did the primary cultures, but the stimulation caused by 5-bromo-2'-deoxyuridine addition was much greater. 4. The affected enzyme was apparently localized in the plasma membrane of the cells with its active centre exposed to the outer environment [ecto-(ATPase) dependent on Ca2+ or Mg2+].5. The activity was unaffected by treatment with p-chloromercuriphenylsulphonate, ouabain andverapamil. 6. Ecto (5'-nucleotidase) activity was not increased by 5-bromo-2'-deoxyuridine treatment of cells, and ecto-(p-nitrophenyl phosphatase) activity was only slightly enhanced.

The gene tinman is required for specification of the heart and visceral muscles in Drosophila

Development ◽  
1993 ◽  
Vol 118 (3) ◽  
pp. 719-729 ◽  
Author(s):  
R. Bodmer
Keyword(s):  
Heart Development ◽  
Body Wall ◽  
Heart Cells ◽  
Visceral Muscle ◽  
Visceral Mesoderm ◽  
Body Wall Muscles ◽  
Visceral Muscles

The homeobox-containing gene tinman (msh-2, Bodmer et al., 1990 Development 110, 661–669) is expressed in the mesoderm primordium, and this expression requires the function of the mesoderm determinant twist. Later in development, as the first mesodermal subdivisions are occurring, expression becomes limited to the visceral mesoderm and the heart. Here, I show that the function of tinman is required for visceral muscle and heart development. Embryos that are mutant for the tinman gene lack the appearance of visceral mesoderm and of heart primordia, and the fusion of the anterior and posterior endoderm is impaired. Even though tinman mutant embryos do not have a heart or visceral muscles, many of the somatic body wall muscles appear to develop although abnormally. When the tinman cDNA is ubiquitously expressed in tinman mutant embryos, via a heatshock promoter, formation of heart cells and visceral mesoderm is partially restored, tinman seems to be one of the earliest genes required for heart development and the first gene reported for which a crucial function in the early mesodermal subdivisions has been implicated.

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