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

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.

2021 ◽  
Vol 6 (4) ◽  
pp. 165-170
Author(s):  
Dr Chrysanthus Chukwuma Sr

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.


Author(s):  
Алексей Дмитриевич Акишин ◽  
Иван Павлович Семчук ◽  
Александр Петрович Николаев

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


1992 ◽  
Vol 27 (4) ◽  
pp. 833-844 ◽  
Author(s):  
Micheline Hanna

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.


Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 212
Author(s):  
Katharina Amschler ◽  
Michael P. Schön

Cancer comprises a large group of complex diseases which arise from the misrouted interplay of mutated cells with other cells and the extracellular matrix. The extracellular matrix is a highly dynamic structure providing biochemical and biophysical cues that regulate tumor cell behavior. While the relevance of biochemical signals has been appreciated, the complex input of biophysical properties like the variation of ligand density and distribution is a relatively new field in cancer research. Nanotechnology has become a very promising tool to mimic the physiological dimension of biophysical signals and their positive (i.e., growth-promoting) and negative (i.e., anti-tumoral or cytotoxic) effects on cellular functions. Here, we review tumor-associated cellular functions such as proliferation, epithelial-mesenchymal transition (EMT), invasion, and phenotype switch that are regulated by biophysical parameters such as ligand density or substrate elasticity. We also address the question of how such factors exert inhibitory or even toxic effects upon tumor cells. We describe three principles of nanostructured model systems based on block copolymer nanolithography, electron beam lithography, and DNA origami that have contributed to our understanding of how biophysical signals direct cancer cell fate.


1987 ◽  
Vol 9 (1) ◽  
pp. 57-61
Author(s):  
Toshiro Sato ◽  
Akihiro Takeuchi ◽  
Jun Yamagami ◽  
Hareaki Yamamoto ◽  
Shigeaki Akiyama ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joseph T. Marmerstein ◽  
Grant A. McCallum ◽  
Dominique M. Durand

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”.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 557
Author(s):  
Stephanie D. Burr ◽  
James A. Stewart

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.


1998 ◽  
Vol 275 (3) ◽  
pp. R677-R682 ◽  
Author(s):  
Susan R. Kayar ◽  
Terry L. Miller ◽  
Meyer J. Wolin ◽  
Eugenia O. Aukhert ◽  
Milton J. Axley ◽  
...  

We present a method for reducing the risk of decompression sickness (DCS) in rats exposed to high pressures of H2. Suspensions of the human colonic microbe Methanobrevibacter smithii were introduced via a colonic cannula into the large intestines of the rats. While the rats breathed H2in a hyperbaric chamber, the microbe metabolized some of the H2diffusing into the intestine, converting H2and CO2to methane and water. Rate of release of methane from the rats, which was monitored by gas chromatography, varied with chamber H2pressure. This rate was higher during decompression than during compression, suggesting that during decompression the microbe was metabolizing H2stored in the rats’ tissues. Rats treated with M. smithii had a 25% (5 of 20) incidence of DCS, which was significantly lower ( P < 0.01) than the 56% (28 of 50) incidence of untreated controls, brought on by a standardized compression and decompression sequence. Thus using a microbe in the intestine to remove an estimated 5% of the body burden of H2reduced DCS risk by more than one-half. This method of biochemical decompression may potentially facilitate human diving.


Author(s):  
Tanuka Datta ◽  
Andrew J. Lee ◽  
Rachel Cain ◽  
Melissa McCarey ◽  
David J. Whellan

AbstractObesity is a growing worldwide epidemic with significant economic burden that carries with it impacts on every physiologic system including the cardiovascular system. Specifically, the risk of heart failure has been shown to increase dramatically in obese individuals. The purpose of this review is to provide background on the individual burdens of heart failure and obesity, followed by exploring proposed physiologic mechanisms that interconnect these conditions, and furthermore introduce treatment strategies for weight loss focusing on bariatric surgery. Review of the existing literature on patients with obesity and heart failure who have undergone bariatric surgery is presented, compared, and contrasted.


2021 ◽  
Vol 12 (1) ◽  
pp. 20-25
Author(s):  
Paula Anderson

There are six electrolytes that are important in maintaining homeostasis within the body. They play vital roles in regulating neurological, myocardial, muscular and cellular functions and are involved in fluid and acid–base balance. Recognising and treating electrolyte derangements is an important role for veterinary nurses especially in emergency and critical care patients. This series of two articles will discuss the physiology behind each of the six major electrolytes and discuss to monitor and treat any abnormalities.


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