scholarly journals Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Yuanyuan Zhao ◽  
Xiaoxian Sun ◽  
Wenming Cao ◽  
Jie Ma ◽  
Li Sun ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Systolic Function ◽  
Tube Formation ◽  
Human Umbilical Cord ◽  
Myocardial Cells ◽  
Ea.Hy926 Cells ◽  
And Migration ◽  
Cardiac Systolic Function

This study is aimed at investigating whether human umbilical cord mesenchymal stem cell- (hucMSC-) derived exosomes (hucMSC-exosomes) have a protective effect on acute myocardial infarction (AMI). Exosomes were characterized under transmission electron microscopy and the particles of exosomes were further examined through nanoparticle tracking analysis. Exosomes (400 μg protein) were intravenously administrated immediately following ligation of the left anterior descending (LAD) coronary artery in rats. Cardiac function was evaluated by echocardiography and apoptotic cells were counted using TUNEL staining. The cardiac fibrosis was assessed using Masson’s trichrome staining. The Ki67 positive cells in ischemic myocardium were determined using immunohistochemistry. The effect of hucMSC-exosomes on blood vessel formation was evaluated through tube formation and migration of human umbilical vein endothelial cells (EA.hy926 cells). The results indicated that ligation of the LAD coronary artery reduced cardiac function and induced cardiomyocyte apoptosis. Administration of hucMSC-exosomes significantly improved cardiac systolic function and reduced cardiac fibrosis. Moreover, hucMSC-exosomes protected myocardial cells from apoptosis and promoted the tube formation and migration of EA.hy926 cells. It is concluded that hucMSC-exosomes improved cardiac systolic function by protecting myocardial cells from apoptosis and promoting angiogenesis. These effects of hucMSC-exosomes might be associated with regulating the expression of Bcl-2 family.

scholarly journals Exercise intolerance in volume overload heart failure is associated with low carotid body mediated chemoreflex drive

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
David C. Andrade ◽  
Esteban Díaz-Jara ◽  
Camilo Toledo ◽  
Karla G. Schwarz ◽  
Katherin V. Pereyra ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Training Program ◽  
Carotid Body ◽  
Exercise Tolerance ◽  
Systolic Function ◽  
Volume Overload ◽  
Exercise Intolerance ◽  
Ventilatory Responses ◽  
Cardiac Systolic Function

AbstractMounting an appropriate ventilatory response to exercise is crucial to meeting metabolic demands, and abnormal ventilatory responses may contribute to exercise-intolerance (EX-inT) in heart failure (HF) patients. We sought to determine if abnormal ventilatory chemoreflex control contributes to EX-inT in volume-overload HF rats. Cardiac function, hypercapnic (HCVR) and hypoxic (HVR) ventilatory responses, and exercise tolerance were assessed at the end of a 6 week exercise training program. At the conclusion of the training program, exercise tolerant HF rats (HF + EX-T) exhibited improvements in cardiac systolic function and reductions in HCVR, sympathetic tone, and arrhythmias. In contrast, HF rats that were exercise intolerant (HF + EX-inT) exhibited worse diastolic dysfunction, and showed no improvements in cardiac systolic function, HCVR, sympathetic tone, or arrhythmias at the conclusion of the training program. In addition, HF + EX-inT rats had impaired HVR which was associated with increased arrhythmia susceptibility and mortality during hypoxic challenges (~ 60% survival). Finally, we observed that exercise tolerance in HF rats was related to carotid body (CB) function as CB ablation resulted in impaired exercise capacity in HF + EX-T rats. Our results indicate that: (i) exercise may have detrimental effects on cardiac function in HF-EX-inT, and (ii) loss of CB chemoreflex sensitivity contributes to EX-inT in HF.

scholarly journals Exercise Intolerance in Volume Overload Heart Failure Is Associated With Low Carotid Body Chemosensitivity

2021 ◽  
Author(s):  
David Andrade ◽  
Esteban Diaz ◽  
Camilo Toledo ◽  
Karla Schwarz ◽  
Katherin Pereyra ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Carotid Body ◽  
Exercise Tolerance ◽  
Systolic Function ◽  
Volume Overload ◽  
Sympathetic Tone ◽  
Exercise Intolerance ◽  
Ventilatory Responses ◽  
Exercise Training Program ◽  
Cardiac Systolic Function

Abstract Mounting an appropriate ventilatory response to exercise is crucial to meeting metabolic demands during exercise and abnormal ventilatory responses may contribute to exercise-intolerance (EX-inT) in HF patients. We sought to determine if abnormal ventilatory chemoreflex control contributes to EX-inT in volume-overload HF rats. Cardiac function, hypercapnic (HCVR) and hypoxic (HVR) ventilatory responses and exercise tolerance were assessed at the end of a 6 weeks exercise training program. Exercise tolerant HF rats (HF+EX-T) completed all training sessions and benefit from exercise as evidenced by improvements in cardiac systolic function and reductions in HCVR, sympathetic tone and arrhythmias. Contrarily, HF rats that failed to complete training sessions (HF+EX-inT) showed no improvements in cardiac systolic function nor in HCVR, sympathetic tone, or arrhythmias but displayed a further compromise in cardiac diastolic function when compared to HF-sedentary rats. In addition, HF+EX-inT rats showed impaired HVR which was associated with increased arrhythmias susceptibility and mortality during hypoxic challenges (~60% survival). Finally, exercise tolerance was closely dependent on carotid body (CB) function since their selective ablation impaired exercise capacity in HF. Our results indicate that: i) exercise may have detrimental effects on cardiac function in HF-EX-inT, and ii) reduced CB chemoreflex contributes to EX-inT in HF.

scholarly journals Neutrophil PAD4 negatively influences cardiac function and remodeling with increasing age

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Van Bruggen ◽  
J Van Wauwe ◽  
P Carai ◽  
L Frederix ◽  
L Vangilbergen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Essential Gene ◽  
Heart Function ◽  
Systolic Function ◽  
Natural Aging ◽  
Collagen Deposition ◽  
National Budget ◽  
Age Related

Abstract Background Aging can be viewed as a status of chronic inflammation, in which neutrophils have a lower threshold for activation. The enzyme peptidylarginine deiminase 4 (PAD4), which catalyzes the conversion of arginine to citrulline, will be activated in a certain population of neutrophils. When this conversion takes place on the histones, neutrophils can form neutrophil extracellular traps (NETs), which are both prothrombotic and proinflammatory. Mice lacking this enzyme systemically were previously reported to be protected from age-related fibrosis. Purpose We aimed to study the long-term effect of neutrophils on cardiac health during the process of natural aging. We hypothesized that neutrophil PAD4, and in consequence NETs, are involved in cardiac fibrosis development, which in turn will result in impaired cardiac function. Methods We generated a mouse model of impaired NET release capability via deletion of PAD4, a NET-essential gene, under the neutrophil-specific promoter (PAD4fl/flMRP8Cre+). In order to study heart failure (HF) development, these specific deletion mice and their littermate controls were aged for a period of two years (coinciding with approximately 70 years of age in the human population; the age at which HF is the number one cause of hospitalization), after which cardiac function and remodeling were evaluated by echocardiography and histology, respectively. A separate set of young mice (12 weeks) were evaluated in parallel. Results We performed a comprehensive echocardiography analysis including both structural and functional parameters. As for systolic function, we could see that in old wild type (WT) mice, ejection fraction (EF) significantly decreased as compared to EF in young and healthy (YH) mice (YH - 67±6%, WT - 53±10%; p<0.0001) (Figure 1B). However, this decrease in systolic function was absent in the old PAD4fl/flMRP8Cre+ mice, with EF being comparable to the YH group (PAD4fl/flMRP8Cre+ - 67±7%; p=0.9169) (figure 1 A,B). As for diastolic function, again we could see a marked decrease in E/A ratio in the WT as compared to the YH population (YH- 1.50±0.23, WT – 1.21±0.17; p<0.0001), while this functional deterioration was absent in aged PAD4fl/flMRP8Cre+ animals (PAD4fl/flMRP8Cre+ - 1.38±0.21; p=0.0837) (Figure 1 C,D). To link this decline in heart function to tissue remodeling, we quantified collagen deposition in the heart. We saw that natural aging resulted in an increase in cardiac collagen deposition in the WT population as compared to YH mice (YH – 0.86±0.63%, WT – 4.02±1.71%). This increased collagen deposition was absent in the neutrophil deletion mice (PAD4fl/flMRP8Cre+ - 1.7±0.76%). Additionally, when comparing WT to PAD4 deletion-mice, we saw that the increase in collagen deposition is significantly higher in the WT mice (p<0.0001). Conclusion Our data confirms neutrophil PAD4 involvement in heart failure progression by promoting cardiac fibrosis, resulting in cardiac dysfunction. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek (FWO) - Vlaanderen

scholarly journals Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jinjuan Fu ◽  
Yuanjuan Tang ◽  
Zhen Zhang ◽  
Lin Tong ◽  
Rongchuan Yue ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Cardiac Function ◽  
Protective Effect ◽  
Tube Formation ◽  
Border Zone ◽  
Cardiomyocyte Proliferation ◽  
Human Coronary Artery ◽  
Plasma Gastrin

Abstract Background It is known that increased gastrin concentration is negatively correlated with cardiovascular mortality, and plasma gastrin levels are increased in patients after myocardial infarction (MI). However, whether gastrin can play a protective role in MI remains unknown. Methods Adult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery (LAD) and subcutaneous infusion of gastrin (120 μg/Kg body weight/day, 100 μL in the pump) for 28 days after MI. Plasma gastrin concentrations were measured through an ELISA detection kit. Mice were analyzed by echocardiography after surgery. CD31 and VEGF expression were quantified using immunofluorescence staining or/and western blot to assess the angiogenesis in peri-infarct myocardium. Capillary-like tube formation and cell migration assays were performed to detect gastrin-induced angiogenesis. Results We found that gastrin administration significantly ameliorated MI-induced cardiac dysfunction and reduced fibrosis at 28 days in post-MI hearts. Additionally, gastrin treatment significantly decreased cardiomyocyte apoptosis and increased angiogenesis in the infarct border zone without influencing cardiomyocyte proliferation. In vitro results revealed that gastrin up-regulated the PI3K/Akt/vascular endothelial growth factor (VEGF) signaling pathway and promoted migration and tube formation of human coronary artery endothelial cells (HCAECs). Cholecystokinin 2 receptor (CCK2R) mediated the protective effect of gastrin since the CCK2R blocker CI988 attenuated the gastrin-mediated angiogenesis and cardiac function protection. Conclusion Our data revealed that gastrin promoted angiogenesis and improved cardiac function in post-MI mice, highlighting its potential as a therapeutic target candidate.

Abstract P319: SARM1 NAD Hydrolase Deficiency Protects Hearts Against Diabetic Cardiomyopathy

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Christine Light ◽  
Chi Fung Lee
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Systolic Function ◽  
Whole Body ◽  
Male Mice ◽  
Progressive Decline ◽  
Nad Synthesis ◽  
Nad Depletion

NAD depletion is associated with the pathogenesis of diseases such as heart failure. Strategies to replenish cellular NAD levels by activating NAD synthesis pathways have shown promises to treat heart disease. However, how NAD consumption mechanisms lead to NAD depletion are less understood. SARM1 is a novel intracellular NAD hydrolase that degrades NAD and promotes axonal degeneration in neurons. We recently showed that NAD redox imbalance and depletion promote the progression of diabetic cardiomyopathy. Therefore, we hypothesized that SARM1 deficiency might protect hearts against diabetic cardiomyopathy. 16-week diabetic stress initiated by streptozotocin (STZ) injections was applied to wild-type C57BL/6 (WT) and whole-body SARM1-KO mice. Cardiac function was measured after 8-week or 16-week of diabetic stress, and cardiac tissue and plasma samples from these mice were harvested after 16 weeks of diabetes. SARM1 mRNA or protein levels were suppressed in SARM1-KO hearts. STZ induced similar hyperglycemia (~600 mg/dL) in both WT and SARM1-KO male mice after 16 weeks. Chronic diabetic stress led to progressive decline in systolic function (Baseline fractional shortening: 50%; 16-week diabetes: 35%; P<0.05; n=5) in WT male mice, which was ameliorated in SARM1-KO male mice (16-week diabetes: 48%; P<0.05; n=5). Progressive decline in diastolic function induced by chronic diabetes (Baseline WT E’/A’: 1.53; WT 16-week diabetes: 1.12; n=5) was also improved in diabetic SARM1-KO mice (KO E’/A’ ratio at 16-week diabetes: 1.5; P<0.05; n=5). Heart weights were similar in diabetic WT or diabetic SARM1-KO hearts. A similar study is on-going in a female cohort. Despite loss of SARM1 expression, no compensatory changes in expressions of other NAD hydrolases (i.e. Cd38 or Bst1) were observed in diabetic SARM1-KO hearts, while expression levels of genes related to NAD consumption and synthesis pathways were mostly unchanged except Qprt and Haao. Cardiac fibrosis was induced in diabetic WT hearts and were suppressed in diabetic SARM1-KO hearts after 16-week diabetic stress, but these changes were not observed in tissues harvested after 8-week diabetic stress. The results suggest fibrosis is a later event in the progression of diabetic cardiomyopathy. WT and SARM1-KO mice have also been challenged with high fat diet feeding (HFD) for 16 weeks, and increased fasting glucose levels and body weights were similarly observed in HFD-WT and HFD-SARM1-KO mice. Longitudinal cardiac function analyses are on-going. Our data thus far support the protective role of SARM1 deficiency in metabolic stress-induced cardiomyopathy, while pathogenic mechanisms of SARM1 in diabetic hearts remain to be determined.

Cardiac function during heat stress: impact of short-term passive heat acclimation

2020 ◽  
Vol 319 (4) ◽  
pp. H753-H764
Author(s):  
Lukas D. Trachsel ◽  
Hadiatou Barry ◽  
Hugo Gravel ◽  
Parya Behzadi ◽  
Christine Henri ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heat Stress ◽  
Cardiac Function ◽  
Systolic Function ◽  
Heat Exposure ◽  
Heat Acclimation ◽  
Passive Heating ◽  
Lower Heart Rate ◽  
Short Term ◽  
Cardiac Systolic Function

A lower heart rate during heat exposure is a classic marker of heat acclimation (HA). It remains unknown if improved cardiac function contributes to this response. A 7-day passive HA protocol did not alter cardiac systolic function during passive heating, whereas it improved some indexes of diastolic function in young adults. Nonetheless, heart rate during heating was unaffected by HA. These results suggest that passive HA induces limited adaptations in cardiac function during passive heating.

An Atypical Presentation of Acute Coronary Syndrome

2012 ◽  
Vol 8 (1) ◽  
pp. 67
Author(s):  
Syed Khurram Mushtaq Gardezi ◽  
Keyword(s):  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Systolic Function ◽  
Artery Bypass ◽  
Left Ventricular Systolic Function ◽  
Regional Wall Motion ◽  
Dobutamine Stress ◽  
Left Ventricular ◽  
Ventricular Systolic Function ◽  
Coronary Syndrome

A 61-year-old man was admitted to hospital with severe occipital headache and weakness and numbness of the left arm. His electrocardiograms showed changes hinting at acute coronary syndrome (ACS). However, in view of his clinical presentation, he underwent tests for likely subarachnoid haemorrhage, but this was ruled out. The next day, he was referred to cardiology. A transthoracic echocardiogram showed reduced left ventricular systolic function along with regional wall motion abnormalities involving inferoposterior walls. The patient was treated as per the protocol for ACS. A dobutamine stress echocardiogram confirmed inferior myocardial infarction with evidence of myocardial viability in the affected left ventricular segments. Subsequent investigations confirmed three-vessel coronary artery disease and reduced left ventricular systolic function. The patient underwent successful coronary artery bypass grafting.

scholarly journals Panax notoginseng saponins promote endothelial progenitor cell angiogenesis via the Wnt/β-catenin pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Peiqi Zhu ◽  
Weidong Jiang ◽  
Shixi He ◽  
Tao Zhang ◽  
Fengchun Liao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Panax Notoginseng ◽  
Tube Formation ◽  
Optimal Concentration ◽  
Mrna Levels ◽  
Panax Notoginseng Saponins ◽  
Endothelial Progenitor ◽  
Angiogenic Potential ◽  
Craniomaxillofacial Surgery ◽  
And Migration

Abstract Background Distraction osteogenesis (DO) is an effective treatment in craniomaxillofacial surgery. However, the issue of sufficient blood supply at the regeneration tissue has limited its wide application. Panax notoginseng saponins (PNS) is a Traditional Chinese Medicine that is commonly used to treat a range of angiogenic diseases. However, the mechanisms whereby PNS alters angiogenesis in endothelial progenitor cells (EPCs) have yet to be clarified. Methods EPCs were identified by immunofluorescence, confirmed by their uptake of fluorescently labeled Dil-ac-LDL and FITC-UEA-1. EPCs were treated with different concentrations of PNS, and the effects of PNS on cell proliferation were measured on the optimal concentration of PNS determined. The effects of PNS on angiogenesis and migration, angiogenic cytokines mRNA expression and the proteins of the Wnt pathway were investigated. Then knocked down β-catenin in EPCs and treated with the optimum concentrational PNS, their angiogenic potential was evaluated in tube formation and migration assays. In addition, the expression of cytokines associated with angiogenesis and Wnt/β-catenin was then assessed via WB and RT-qPCR. Results We were able to determine the optimal concentration of PNS in the promotion of cell proliferation, tube formation, and migration to be 6.25 mg/L. PNS treatment increased the mRNA levels of VEGF, bFGF, VE-Cadherin, WNT3a, LRP5, β-catenin, and TCF4. After knocked down β-catenin expression, we found that PNS could sufficient to partially reverse the suppression of EPC angiogenesis. Conclusions Overall, 6.25 mg/L PNS can promote EPC angiogenesis via Wnt/β-catenin signaling pathway activation.

Conditioned medium from the human umbilical cord-mesenchymal stem cells stimulate the proliferation of human keratinocytes

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Sushmitha Sriramulu ◽  
Antara Banerjee ◽  
Ganesan Jothimani ◽  
Surajit Pathak
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Umbilical Cord ◽  
Human Keratinocytes ◽  
Human Umbilical Cord ◽  
Hacat Cells ◽  
And Migration

AbstractObjectivesWound healing is a complex process with a sequence of restoring and inhibition events such as cell proliferation, differentiation, migration as well as adhesion. Mesenchymal stem cells (MSC) derived conditioned medium (CM) has potent therapeutic functions and promotes cell proliferation, anti-oxidant, immunosuppressive, and anti-apoptotic effects. The main aim of this research is to study the role of human umbilical cord-mesenchymal stem cells (UC-MSCs) derived CM in stimulating the proliferation of human keratinocytes (HaCaT).MethodsFirstly, MSC were isolated from human umbilical cords (UC) and the cells were then cultured in proliferative medium. We prepared and collected the CM after 72 h. Morphological changes were observed after the treatment of HaCaT cells with CM. To validate the findings, proliferation rate, clonal efficiency and also gene expression studies were performed.ResultsIncreased proliferation rate was observed and confirmed with the expression of Proliferating Cell Nuclear Antigen (PCNA) after treatment with HaCaT cells. Cell-cell strap formation was also observed when HaCaT cells were treated with CM for a period of 5–6 days which was confirmed by the increased expression of Collagen Type 1 Alpha 1 chain (Col1A1).ConclusionsOur results from present study depicts that the secretory components in the CM might play a significant role by interacting with keratinocytes to promote proliferation and migration. Thus, the CM stimulates cellular proliferation, epithelialization and migration of skin cells which might be the future promising application in wound healing.

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