scholarly journals Exploring the complex interplay in the regulation of cardiac pathophysiological functions by protein kinases and phosphatases

2021 ◽  
Vol 6 (4) ◽  
pp. 165-170
Author(s):  
Dr Chrysanthus Chukwuma Sr
Keyword(s):  
Heart Failure ◽  
Cardiovascular System ◽  
Protein Kinases ◽  
Body Burden ◽  
The Body ◽  
Complex Interplay ◽  
Physiological Processes ◽  
Progressive Heart Failure ◽  
Drug Lead ◽  
Cardiac Excitation

Cardiovascular disease manifests as an intricately complex entity presenting as a derangement of the cardiovascular system. Cardiac or heart failure connotes the pathophysiological state in which deficient cardiac output compromises the body burden and requirements. Protein kinases regulate several pathophysiological processes and are emerging targets for drug lead or discovery. The protein kinases are family members of the serine/threonine phosphatases. Protein kinases and phosphatases are pivotal in the regulatory mechanisms in the reversible phosphorylation of diverse effectors whereby discrete signaling molecules regulate cardiac excitation and contraction. Protein phosphorylation is critical for the sustenance of cardiac functionalities. The two major contributory ingredients to progressive myocardium derangement are dysregulation of Ca2+processes and contemporaneous elevated concentrations of reactive oxygen species, ROS. Certain cardiac abnormalities include cardiac myopathy or hypertrophy due to response in untoward haemodynamic demand with concomitant progressive heart failure. The homeostasis or equilibrium between protein kinases and phosphatases influence cardiac morphology and excitability during pathological and physiological processes of the cardiovascular system.

scholarly journals The complex interplay in the regulation of cardiac pathophysiologic functionalities by protein kinases and phosphatases

2021 ◽  
Vol 6 (3) ◽  
pp. 048-054
Author(s):  
Chukwuma Sr Chrysanthus
Keyword(s):  
Heart Failure ◽  
Protein Phosphorylation ◽  
Cardiovascular System ◽  
Protein Kinases ◽  
Cell Fate ◽  
Body Burden ◽  
The Body ◽  
Discrete Control ◽  
Cellular Functions ◽  
Cardiac Excitation

Protein phosphorylation regulates several dimensions of cell fate and is substantially dysregulated in pathophysiological instances as evident spatiotemporally via intracellular localizations or compartmentalizations with discrete control by specific kinases and phosphatases. Cardiovascular disease manifests as an intricately complex entity presenting as a derangement of the cardiovascular system. Cardiac or heart failure connotes the pathophysiological state in which deficient cardiac output compromises the body burden and requirements. Protein kinases regulate several pathophysiological processes and are emerging targets for drug lead or discovery. The protein kinases are family members of the serine/threonine phosphatases. Protein kinases covalently modify proteins by attaching phosphate groups from ATP to residues of serine, threonine and/or tyrosine. Protein kinases and phosphatases are pivotal in the regulatory mechanisms in the reversible phosphorylation of diverse effectors whereby discrete signaling molecules regulate cardiac excitation and contraction. Protein phosphorylation is critical for the sustenance of cardiac functionalities. The two major contributory ingredients to progressive myocardium derangement are dysregulation of Ca2+ processes and contemporaneous elevated concentrations of reactive oxygen species, ROS. Certain cardiac abnormalities include cardiac myopathy or hypertrophy due to response in untoward haemodynamic demand with concomitant progressive heart failure. The homeostasis or equilibrium between protein kinases and phosphatases influence cardiac morphology and excitability during pathological and physiological processes of the cardiovascular system. Inasmuch as protein kinases regulate numerous dimensions of normal cellular functions, the pathophysiological dysfunctionality of protein kinase signaling pathways undergirds the molecular aspects of several cardiovascular diseases or disorders as related in this study. These have presented protein kinases as essential and potential targets for drug discovery and heart disease therapy.

scholarly journals Re-evaluating functional landscape of the cardiovascular system during development

2017 ◽  
Author(s):  
Norio Takada ◽  
Madoka Omae ◽  
Fumihiko Sagawa ◽  
Neil C. Chi ◽  
Satsuki Endo ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Model Organism ◽  
Wide Distribution ◽  
The Body ◽  
Physiological Processes ◽  
Organ Specific ◽  
Vertebrate Model ◽  
Underlying Mechanisms ◽  
And Function ◽  
Cardiovascular Functions

ABSTRACTThe cardiovascular system facilitates body-wide distribution of oxygen, a vital process for development and survival of virtually all vertebrates. However, zebrafish, a vertebrate model organism, appears to form organs and survive mid-larval periods without the functional cardiovascular system. Despite such dispensability, it is the first organ to develop. Such enigma prompted us to hypothesize yet other cardiovascular functions that are important for developmental and/or physiological processes. Hence, systematic cellular ablations and functional perturbations are performed on zebrafish cardiovascular system to gain comprehensive and body-wide understanding of such functions and to elucidate underlying mechanisms. This approach identifies a set of organ-specific genes, each implicated for important functions. The study also unveils distinct cardiovascular mechanisms, each differentially regulating their expressions in organ-specific and oxygen-independent manners. Such mechanisms are mediated by organ-vessel interactions, circulation-dependent signals, and circulation-independent beating-heart-derived signals. Hence, a comprehensive and body-wide functional landscape of the cardiovascular system reported herein may provide a clue as to why it is the first organ to develop. Furthermore, the dataset herein could serve as a resource for the study of organ development and function.SUMMARY STATEMENTThe body-wide landscape of the cardiovascular functions during development is reported. Such landscape may provide a clue as to why the cardiovascular system is the first organ to develop.

scholarly journals Iron Deficiency in Heart Failure: Mechanisms and Pathophysiology

2021 ◽  
Vol 11 (1) ◽  
pp. 125
Author(s):  
Ridha I. S. Alnuwaysir ◽  
Martijn F. Hoes ◽  
Dirk J. van Veldhuisen ◽  
Peter van der Meer ◽  
Niels Grote Beverborg
Keyword(s):  
Quality Of Life ◽  
Heart Failure ◽  
Iron Deficiency ◽  
Exercise Capacity ◽  
Iron Homeostasis ◽  
Current Knowledge ◽  
The Body ◽  
Physiological Processes ◽  
Underlying Causes

Iron is an essential micronutrient for a myriad of physiological processes in the body beyond erythropoiesis. Iron deficiency (ID) is a common comorbidity in patients with heart failure (HF), with a prevalence reaching up to 59% even in non-anaemic patients. ID impairs exercise capacity, reduces the quality of life, increases hospitalisation rate and mortality risk regardless of anaemia. Intravenously correcting ID has emerged as a promising treatment in HF as it has been shown to alleviate symptoms, improve quality of life and exercise capacity and reduce hospitalisations. However, the pathophysiology of ID in HF remains poorly characterised. Recognition of ID in HF triggered more research with the aim to explain how correcting ID improves HF status as well as the underlying causes of ID in the first place. In the past few years, significant progress has been made in understanding iron homeostasis by characterising the role of the iron-regulating hormone hepcidin, the effects of ID on skeletal and cardiac myocytes, kidneys and the immune system. In this review, we summarise the current knowledge and recent advances in the pathophysiology of ID in heart failure, the deleterious systemic and cellular consequences of ID.

DEVELOPMENT OF A DEVICE FOR CONTROL OF THE STATE OF THE ORGANISM BASED ON PHOTOPLETISMOGRAPHY USING TECHNOLOGIES OF DIGITAL ADAPTIVE FILTRATION

2020 ◽  
pp. 100-107
Author(s):  
Алексей Дмитриевич Акишин ◽  
Иван Павлович Семчук ◽  
Александр Петрович Николаев
Keyword(s):  
Heart Rate ◽  
Cardiovascular System ◽  
Adaptive Filtering ◽  
Least Squares Method ◽  
Optimal Algorithm ◽  
Heart Diseases ◽  
Cardiac Activity ◽  
Motion Artifacts ◽  
The Body ◽  
Advantages And Disadvantages

Постоянно растущий интерес к разработке новых неинвазивных и безманжетных методов измерения параметров сердечной деятельности, использование которых давало бы возможность непрерывного и удаленного контроля сердечно-сосудистой системы, обуславливает актуальность данной работы. В многочисленных публикациях продолжаются обсуждения преимуществ и недостатков различных методов ранней диагностики сердечно-сосудистых заболеваний. Однако артефакты движения являются сильной помехой, мешающей точной оценке показателей функционирования сердечно-сосудистой системы. Одним из перспективных методов контроля является метод оценки физиологических параметров с использованием фотоплетизмографии. Данная статья посвящена разработке устройства для фотоплетизмографических исследований и алгоритмических методов обработки регистрируемых сигналов для обеспечения мониторинга сердечного ритма с заданной точностью. В работе используются технологии цифровой адаптивной фильтрации полученных сигналов для мониторинга сердечного ритма в условиях внешних механических и электрических помеховых воздействий, ухудшающих точностные характеристики системы, а также разработана архитектура системы и изготовлен макет устройства, который позволил провести измерения для определения оптимального алгоритма цифровой обработки сигналов. При использовании устройства применялись методы адаптивной фильтрации на основе фильтров Винера, фильтров на основе метода наименьших квадратов и Калмановской фильтрации. Разработанное устройство для фотоплетизмографических исследований обеспечило возможность мониторинга сердечного ритма с заданной точностью, контроля текущего состояния организма и может быть использовано в качестве средства диагностики заболеваний сердца The constantly growing interest in the development of new non-invasive and cuff-free methods for measuring the parameters of cardiac activity, the use of which would give the possibility of continuous and remote monitoring of the cardiovascular system, determines the relevance of this work. Numerous publications continue to discuss the advantages and disadvantages of various methods of early diagnosis of cardiovascular disease. However, motion artifacts are a strong hindrance to the accurate assessment of the performance of the cardiovascular system. One of the promising control methods is the method for assessing physiological parameters using photoplethysmography. This article is devoted to the development of a device for photoplethysmographic studies and algorithmic methods for processing recorded signals to ensure monitoring of the heart rate with a given accuracy. The work uses technologies of digital adaptive filtering of the received signals to monitor the heart rate in conditions of external mechanical and electrical interference, which worsen the accuracy characteristics of the system, as well as the architecture of the system and a prototype of the device, which made it possible to carry out measurements to determine the optimal algorithm for digital signal processing. When using the device, the methods of adaptive filtering based on Wiener filters, filters based on the least squares method and Kalman filtering were used. The developed device for photoplethysmographic studies provided the ability to monitor the heart rate with a given accuracy, control the current state of the body and can be used as a means of diagnosing heart diseases

Effect of Sample Storage Conditions on Body Burden Analysis of Organic Contaminants in Unionid Mussels

1992 ◽  
Vol 27 (4) ◽  
pp. 833-844 ◽  
Author(s):  
Micheline Hanna
Keyword(s):  
Organic Contaminants ◽  
Body Burden ◽  
Storage Conditions ◽  
The Body ◽  
Sample Storage ◽  
Pcb Congeners ◽  
Unionid Mussels ◽  
Group A ◽  
The Difference ◽  
Group B

Abstract In order to quantitatively assess the effect of sample storage conditions on the body burden analysis of organic contaminants, a comparative analysis was carried out on the unionid mussel Elliptic complanata. The mussels were divided into two groups, each with distinct storage conditions, while Group A was kept in the freezer at −20°C, Group B was kept in the refrigerator for five days at 5°C. All the compounds present in the control were also present in Group B samples. Analysis of the organic contaminants in each of these two groups showed that for total PCB concentrations, the two treatments were not significantly different; however when compared individually 6 of the 13 PCB congeners showed significant differences. The observed differences were relatively small for individual PCB congeners (7.1 to 15.3%), higher for chlorobenzenes (10.5 to 36.4%), and yet higher for HCE (44.1%); the difference for HCE, although large is nevertheless not significant, even if only marginally so.

Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors

2019 ◽  
Vol 25 (26) ◽  
pp. 2892-2905 ◽  
Author(s):  
Sumit Jamwal ◽  
Ashish Mittal ◽  
Puneet Kumar ◽  
Dana M. Alhayani ◽  
Amal Al-Aboudi
Keyword(s):  
Nervous System ◽  
Therapeutic Potential ◽  
The Body ◽  
Membrane Receptors ◽  
Physiological Importance ◽  
Physiological Processes ◽  
Central Nervous Systems ◽  
Energy Consuming ◽  
Metabolic Dysfunctions ◽  
G Protein Coupled

Adenosine is a naturally occurring nucleoside and an essential component of the energy production and utilization systems of the body. Adenosine is formed by the degradation of adenosine-triphosphate (ATP) during energy-consuming processes. Adenosine regulates numerous physiological processes through activation of four subtypes of G-protein coupled membrane receptors viz. A1, A2A, A2B and A3. Its physiological importance depends on the affinity of these receptors and the extracellular concentrations reached. ATP acts as a neurotransmitter in both peripheral and central nervous systems. In the peripheral nervous system, ATP is involved in chemical transmission in sensory and autonomic ganglia, whereas in central nervous system, ATP, released from synaptic terminals, induces fast excitatory postsynaptic currents. ATP provides the energetics for all muscle movements, heart beats, nerve signals and chemical reactions inside the body. Adenosine has been traditionally considered an inhibitor of neuronal activity and a regulator of cerebral blood flow. Since adenosine is neuroprotective against excitotoxic and metabolic dysfunctions observed in neurological and ocular diseases, the search for adenosinerelated drugs regulating adenosine transporters and receptors can be important for advancement of therapeutic strategies against these diseases. This review will summarize the therapeutic potential and recent SAR and pharmacology of adenosine and its receptor agonists and antagonists.

Computer assisted instruction for therapy of heart failure based on simulation of cardiovascular system

1987 ◽  
Vol 9 (1) ◽  
pp. 57-61
Author(s):  
Toshiro Sato ◽  
Akihiro Takeuchi ◽  
Jun Yamagami ◽  
Hareaki Yamamoto ◽  
Shigeaki Akiyama ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular System ◽  
Computer Assisted Instruction ◽  
Computer Assisted ◽  
Assisted Instruction

scholarly journals Direct measurement of vagal tone in rats does not show correlation to HRV

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joseph T. Marmerstein ◽  
Grant A. McCallum ◽  
Dominique M. Durand
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Neural Activity ◽  
Vagal Tone ◽  
Neural Recording ◽  
The Body ◽  
Autonomic Nerve ◽  
Vagal Activity ◽  
Recording Technology

AbstractThe vagus nerve is the largest autonomic nerve, innervating nearly every organ in the body. “Vagal tone” is a clinical measure believed to indicate overall levels of vagal activity, but is measured indirectly through the heart rate variability (HRV). Abnormal HRV has been associated with many severe conditions such as diabetes, heart failure, and hypertension. However, vagal tone has never been directly measured, leading to disagreements in its interpretation and influencing the effectiveness of vagal therapies. Using custom carbon nanotube yarn electrodes, we were able to chronically record neural activity from the left cervical vagus in both anesthetized and non-anesthetized rats. Here we show that tonic vagal activity does not correlate with common HRV metrics with or without anesthesia. Although we found that average vagal activity is increased during inspiration compared to expiration, this respiratory-linked signal was not correlated with HRV either. These results represent a clear advance in neural recording technology but also point to the need for a re-interpretation of the link between HRV and “vagal tone”.

scholarly journals Rap1a Overlaps the AGE/RAGE Signaling Cascade to Alter Expression of α-SMA, p-NF-κB, and p-PKC-ζ in Cardiac Fibroblasts Isolated from Type 2 Diabetic Mice

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 557
Author(s):  
Stephanie D. Burr ◽  
James A. Stewart
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Hydrogen Peroxide ◽  
Cardiac Fibroblasts ◽  
The Body ◽  
Signaling Cascade ◽  
Diabetic Mice ◽  
Pkc Ζ ◽  
Type 2 Diabetic

Cardiovascular disease, specifically heart failure, is a common complication for individuals with type 2 diabetes mellitus. Heart failure can arise with stiffening of the left ventricle, which can be caused by “active” cardiac fibroblasts (i.e., myofibroblasts) remodeling the extracellular matrix (ECM). Differentiation of fibroblasts to myofibroblasts has been demonstrated to be an outcome of AGE/RAGE signaling. Hyperglycemia causes advanced glycated end products (AGEs) to accumulate within the body, and this process is greatly accelerated under chronic diabetic conditions. AGEs can bind and activate their receptor (RAGE) to trigger multiple downstream outcomes, such as altering ECM remodeling, inflammation, and oxidative stress. Previously, our lab has identified a small GTPase, Rap1a, that possibly overlaps the AGE/RAGE signaling cascade to affect the downstream outcomes. Rap1a acts as a molecular switch connecting extracellular signals to intracellular responses. Therefore, we hypothesized that Rap1a crosses the AGE/RAGE cascade to alter the expression of AGE/RAGE associated signaling proteins in cardiac fibroblasts in type 2 diabetic mice. To delineate this cascade, we used genetically different cardiac fibroblasts from non-diabetic, diabetic, non-diabetic RAGE knockout, diabetic RAGE knockout, and Rap1a knockout mice and treated them with pharmacological modifiers (exogenous AGEs, EPAC, Rap1a siRNA, and pseudosubstrate PKC-ζ). We examined changes in expression of proteins implicated as markers for myofibroblasts (α-SMA) and inflammation/oxidative stress (NF-κB and SOD-1). In addition, oxidative stress was also assessed by measuring hydrogen peroxide concentration. Our results indicated that Rap1a connects to the AGE/RAGE cascade to promote and maintain α-SMA expression in cardiac fibroblasts. Moreover, Rap1a, in conjunction with activation of the AGE/RAGE cascade, increased NF-κB expression as well as hydrogen peroxide concentration, indicating a possible oxidative stress response. Additionally, knocking down Rap1a expression resulted in an increase in SOD-1 expression suggesting that Rap1a can affect oxidative stress markers independently of the AGE/RAGE signaling cascade. These results demonstrated that Rap1a contributes to the myofibroblast population within the heart via AGE/RAGE signaling as well as promotes possible oxidative stress. This study offers a new potential therapeutic target that could possibly reduce the risk for developing diabetic cardiovascular complications attributed to AGE/RAGE signaling.

scholarly journals PPARs as Metabolic Sensors and Therapeutic Targets in Liver Diseases

2021 ◽  
Vol 22 (15) ◽  
pp. 8298
Author(s):  
Hugo Christian Monroy-Ramirez ◽  
Marina Galicia-Moreno ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Arturo Santos ◽  
...  
Keyword(s):  
Liver Diseases ◽  
Metabolic Regulation ◽  
Structural Changes ◽  
Critical Role ◽  
The Body ◽  
Molecular Characteristics ◽  
Signal Pathways ◽  
Virus Infections ◽  
Physiological Processes ◽  
Hepatic Level

Carbohydrates and lipids are two components of the diet that provide the necessary energy to carry out various physiological processes to help maintain homeostasis in the body. However, when the metabolism of both biomolecules is altered, development of various liver diseases takes place; such as metabolic-associated fatty liver diseases (MAFLD), hepatitis B and C virus infections, alcoholic liver disease (ALD), and in more severe cases, hepatocelular carcinoma (HCC). On the other hand, PPARs are a family of ligand-dependent transcription factors with an important role in the regulation of metabolic processes to hepatic level as well as in other organs. After interaction with specific ligands, PPARs are translocated to the nucleus, undergoing structural changes to regulate gene transcription involved in lipid metabolism, adipogenesis, inflammation and metabolic homeostasis. This review aims to provide updated data about PPARs’ critical role in liver metabolic regulation, and their involvement triggering the genesis of several liver diseases. Information is provided about their molecular characteristics, cell signal pathways, and the main pharmacological therapies that modulate their function, currently engaged in the clinic scenario, or in pharmacological development.

Sign in / Sign up

Export Citation Format

Share Document