The Role of Potassium Ions in the Control of Heart Function

Author(s):  
Fritz Markwardt
2020 ◽  
Vol 20 (4) ◽  
pp. 318-324 ◽  
Author(s):  
Lei Yang ◽  
Shuoji Zhu ◽  
Yongqing Li ◽  
Jian Zhuang ◽  
Jimei Chen ◽  
...  

Background: Our previous studies have shown that Pygo (Pygopus) in Drosophila plays a critical role in adult heart function that is likely conserved in mammals. However, its role in the differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) into cardiomyocytes remains unknown. Objective: To investigate the role of pygo2 in the differentiation of hUC-MSCs into cardiomyocytes. Methods: Third passage hUC-MSCs were divided into two groups: a p+ group infected with the GV492-pygo2 virus and a p− group infected with the GV492 virus. After infection and 3 or 21 days of incubation, Quantitative real-time PCR (qRT-PCR) was performed to detect pluripotency markers, including OCT-4 and SOX2. Nkx2.5, Gata-4 and cTnT were detected by immunofluorescence at 7, 14 and 21 days post-infection, respectively. Expression of cardiac-related genes—including Nkx2.5, Gata-4, TNNT2, MEF2c, ISL-1, FOXH1, KDR, αMHC and α-Actin—were analyzed by qRT-PCR following transfection with the virus at one, two and three weeks. Results : After three days of incubation, there were no significant changes in the expression of the pluripotency stem cell markers OCT-4 and SOX2 in the p+ group hUC-MSCs relative to controls (OCT-4: 1.03 ± 0.096 VS 1, P > 0.05, SOX2: 1.071 ± 0.189 VS 1, P > 0.05); however, after 21 days, significant decreases were observed (OCT-4: 0.164 ± 0.098 VS 1, P < 0.01, SOX2: 0.209 ± 0.109 VS 1, P < 0.001). Seven days following incubation, expression of mesoderm specialisation markers, such as Nkx2.5, Gata-4, MEF2c and KDR, were increased; at 14 days following incubation, expression of cardiac genes, such as Nkx2.5, Gata-4, TNNT2, MEF2c, ISL-1, FOXH1, KDR, αMHC and α-Actin, were significantly upregulated in the p+ group relative to the p− group (P < 0.05). Taken together, these findings suggest that overexpression of pygo2 results in more hUCMSCs gradually differentiating into cardiomyocyte-like cells. Conclusion: We are the first to show that overexpression of pygo2 significantly enhances the expression of cardiac-genic genes, including Nkx2.5 and Gata-4, and promotes the differentiation of hUC-MSCs into cardiomyocyte-like cells.


Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1002
Author(s):  
Fabiola Marino ◽  
Mariangela Scalise ◽  
Eleonora Cianflone ◽  
Luca Salerno ◽  
Donato Cappetta ◽  
...  

Over the years strong evidence has been accumulated showing that aerobic physical exercise exerts beneficial effects on the prevention and reduction of cardiovascular risk. Exercise in healthy subjects fosters physiological remodeling of the adult heart. Concurrently, physical training can significantly slow-down or even reverse the maladaptive pathologic cardiac remodeling in cardiac diseases, improving heart function. The underlying cellular and molecular mechanisms of the beneficial effects of physical exercise on the heart are still a subject of intensive study. Aerobic activity increases cardiovascular nitric oxide (NO) released mainly through nitric oxidase synthase 3 activity, promoting endothelium-dependent vasodilation, reducing vascular resistance, and lowering blood pressure. On the reverse, an imbalance between increasing free radical production and decreased NO generation characterizes pathologic remodeling, which has been termed the “nitroso-redox imbalance”. Besides these classical evidence on the role of NO in cardiac physiology and pathology, accumulating data show that NO regulate different aspects of stem cell biology, including survival, proliferation, migration, differentiation, and secretion of pro-regenerative factors. Concurrently, it has been shown that physical exercise generates physiological remodeling while antagonizes pathologic remodeling also by fostering cardiac regeneration, including new cardiomyocyte formation. This review is therefore focused on the possible link between physical exercise, NO, and stem cell biology in the cardiac regenerative/reparative response to physiological or pathological load. Cellular and molecular mechanisms that generate an exercise-induced cardioprotective phenotype are discussed in regards with myocardial repair and regeneration. Aerobic training can benefit cells implicated in cardiovascular homeostasis and response to damage by NO-mediated pathways that protect stem cells in the hostile environment, enhance their activation and differentiation and, in turn, translate to more efficient myocardial tissue regeneration. Moreover, stem cell preconditioning by and/or local potentiation of NO signaling can be envisioned as promising approaches to improve the post-transplantation stem cell survival and the efficacy of cardiac stem cell therapy.


2019 ◽  
Vol 128 (06/07) ◽  
pp. 388-394
Author(s):  
Helge Müller-Fielitz ◽  
Markus Schwaninger

AbstractThyroid hormone (TH) regulation is important for development, energy homeostasis, heart function, and bone formation. To control the effects of TH in target organs, the hypothalamus-pituitary-thyroid (HPT) axis and the tissue-specific availability of TH are highly regulated by negative feedback. To exert a central feedback, TH must enter the brain via specific transport mechanisms and cross the blood-brain barrier. Here, tanycytes, which are located in the ventral walls of the 3rd ventricle in the mediobasal hypothalamus (MBH), function as gatekeepers. Tanycytes are able to transport, sense, and modify the release of hormones of the HPT axis and are involved in feedback regulation. In this review, we focus on the relevance of tanycytes in thyrotropin-releasing hormone (TRH) release and review available genetic tools to investigate the physiological functions of these cells.


Author(s):  
Б.И. Кузник ◽  
Ю.Н. Смоляков ◽  
С.О. Давыдов ◽  
Е.С. Гусева ◽  
М.В. Максименя

У женщин, больных гипертонической болезнью, существуют тесные корреляционные взаимосвязи между различными форменными элементами крови и уровнем артериального давления, показателями деятельности сердца, тестами, характеризующими состояние гемодинамики, тромбодинамики и коагуляционной активности крови. Цель исследования - изучение роли различных форменных элементов крови и их соотношения в регуляции уровня эстрогена, прогестерона и пролактина, ТБК-активных продуктов и антиоксидантной активности у больных гипертонической болезнью. Методика. Исследования проведены на 72 больных гипертонической болезнью, контрольную группу составили 12 женщин с нормальным артериальным давлением. Больные были разделены на 2 группы: в 1-ю группу вошли 37 пациенток с гипертонической болезнью II стадии, находящиеся на гипотензивной терапии, 2-ю - составили 35 женщин с гипертонией II стадии, которые кроме медикаментозного лечения, регулярно проходили курсы кинезотерапии на протяжении 2-3 лет. Результаты. Методом корреляционного анализа установлено, что у здоровых женщин и больных гипертонической болезнью, изучаемые взаимосвязи могут носить как однонаправленный, так и разнонаправленный характер. У здоровых женщин обнаруживается прямая связь между количеством лимфоцитов и уровнем прогестерона и обратная - с уровнем пролактина. Прямая связь также выявлена между индексом нейтрофилы/базофилы и прогестероном. При гипертонии у больных 1-й группы обнаруживается прямая связь между количеством эритроцитов и прогестероном, числом эозинофилов и пролактином; индекса лимфоциты/эозинофилы с эстрадиолом; индексов нейтрофилы/моноциты, нейтрофилы/базофилы и лимфоциты/базофилы с прогестероном. Отрицательная корреляция выявляется между индексами нейтрофилы/лимфоциты и нейтрофилы/эозинофилы с пролактином. У больных 2-й группы обнаружены прямые корреляционные связи между абсолютным количеством лейкоцитов, нейтрофилов и эозинофилов и отрицательная связь индекса эритроциты/лейкоциты с пролактином. При оценке корреляционных взаимосвязей показателей крови с показателями активности оксидантно/антиоксидантной системы показано, что у здоровых женщин существуют положительные связи между числом моноцитов с содержанием ТБК-продуктов и активностью антиоксидантной системы; эозинофилов с активностью антиоксидантной системы; индекса лейкоциты/тромбоциты с уровнем ТБК-продуктов. При гипертонической болезни в группе без кинезотерапии (1-я группа) выявлена отрицательная взаимосвязь между общим числом эритроцитов и показателями активности антиоксидантной системы. Заключение. Практически все форменные элементы крови и различные их взаимоотношения у здоровых и больных гипертонической болезнью играют существенную роль в регуляции уровня эстрадиола, прогестерона, пролактина и состояния системы перекисного окисления липидов - антиоксидантная активность. Close correlations exist between different blood cells (BC), blood pressure, heart function, results of hemodynamics tests, thrombodynamics, and blood coagulation in women with hypertension. Aim. The study addressed the role of different BCs and their combinations in regulation of estrogen, progesterone, prolactin, TBA-reactive substances (TBARS), and antioxidant activity (AOA) in hypertensive patients. Methods. The study included 12 healthy women (control) and 72 patients with essential hypertension (EH). Patients with EH were divided into two groups; the first group (EH-1) consisted of 37 women with stage II EH receiving an antihypertensive therapy and the second group (EH-2) consisted of 35 women who, in addition to the drug therapy, yearly underwent 3-4 courses of kinesitherapy for 2-3 year on a regular basis. Results. Both in healthy women and patients of the EH-1 and EH-2 groups, the studied relationships were either positive or negative. In healthy women, LYM positively correlated with progesterone and inversely correlated with prolactin, and the NEU/BAS ratio positively correlated with progesterone. In patients of the EH-1 group, there were positive correlations of RBC with progesterone; EOS with prolactin; and LYM/EOS with estradiol; and NEU/MON, NEU/BAS, and LYM/BAS with progesterone. The NEU/LYM and NEU/EOS ratios inversely correlated with prolactin. In patients of the EH-2 group, there were positive correlations of WBC, NEU, and EOS with prolactin and inverse correlations of the RBC/WBC ratio with prolactin. Evaluation of correlations between blood indexes and the oxidant/antioxidant system showed that in healthy women, there were positive correlations of the MON count with TBARS and AOA; EOS with AOA; and the WBC/PLT ratio with TBARS. Patients of the EH-1 group showed a negative correlation of the total RBC count with AOA. Conclusion. In both healthy subjects and EH groups, almost all BCs and their relationships play a significant role in regulation of estradiol, progesterone, prolactin, and the lipid peroxidation/AOA system.


2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Anchit Bhagat ◽  
eugenie kleinerman ◽  
Eugenie Kleinerman

Doxorubicin (Dox) is one of the most effective chemotherapy agents for treating childhood cancer. Unfortunately, Dox also causes damage to the heart which leads to reduced heart function and heart failure in >50% of survivors. Understanding the mechanisms by which Dox induces cardiotoxicity is crucial to identifying preventive interventions. Inflammation, in particular: neutrophils and monocytes has been linked to other form of cardiac disease. However, the role of these immune cells in Dox-induced cardiotoxicity has not been examined. We hypothesize that neutrophils are responsible for the early damage caused by Dox treatment. Using our mouse cardiotoxicity model, mice were treated with Doxorubicin for 2 weeks. Neutrophil infiltration in the heart 24 hours after therapy were evaluated by flow cytometry. There was an increase in neutrophils in heart tissue of Dox-treated mice as compared to controls and a decrease in heart function as quantified by echocardiography (ejection fraction [EF] and fractional shortening [FS]). Next, we depleted neutrophils using an anti-Ly6G antibody. Neutrophil depletion was confirmed by flow cytometry in the blood and hearts of Dox-treated mice. We found that neutrophil depletion prevented Dox-induced decrease in both ejection fraction and fractional shortening. Additionally, we also observed by flow cytometry that infiltration of monocytes was unaffected by the neutrophil depletion antibody. Based on this data we concluded that neutrophils and not monocytes are integral contributors to acute heart damage caused by Dox. These data indicate that targeting neutrophils may be a preventive strategy against Dox-induced cardiotoxicity.


Sign in / Sign up

Export Citation Format

Share Document