scholarly journals A Bioinformatics Perspective on the Links Between Tetraspanin-Enriched Microdomains and Cardiovascular Pathophysiology

2021 ◽  
Vol 8 ◽  
Author(s):  
Ge Sun ◽  
Junxiong Chen ◽  
Yingjun Ding ◽  
Jonathan D. Wren ◽  
Fuyi Xu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular System ◽  
Target Genes ◽  
Mapk Signaling ◽  
Immunoglobulin Superfamily ◽  
Membrane Domains ◽  
Expression Levels ◽  
Blood Pressure Data ◽  
Human Cardiovascular System ◽  
Cell Adhesion Proteins

Background: Tetraspanins and integrins are integral membrane proteins. Tetraspanins interact with integrins to modulate the dynamics of adhesion, migration, proliferation, and signaling in the form of membrane domains called tetraspanin-enriched microdomains (TEMs). TEMs also contain other cell adhesion proteins like immunoglobulin superfamily (IgSF) proteins and claudins. Cardiovascular functions of these TEM proteins have emerged and remain to be further revealed.Objectives: The aims of this study are to explore the roles of these TEM proteins in the cardiovascular system using bioinformatics tools and databases and to highlight the TEM proteins that may functionally associate with cardiovascular physiology and pathology.Methods: For human samples, three databases—GTEx, NCBI-dbGaP, and NCBI-GEO—were used for the analyses. The dbGaP database was used for GWAS analysis to determine the association between target genes and human phenotypes. GEO is an NCBI public repository that archives genomics data. GTEx was used for the analyses of tissue-specific mRNA expression levels and eQTL. For murine samples, GeneNetwork was used to find gene–phenotype correlations and gene–gene correlations of expression levels in mice. The analysis of cardiovascular data was the focus of this study.Results: Some integrins and tetraspanins, such as ITGA8 and Cd151, are highly expressed in the human cardiovascular system. TEM components are associated with multiple cardiovascular pathophysiological events in humans. GWAS and GEO analyses showed that human Cd82 and ITGA9 are associated with blood pressure. Data from mice also suggest that various cardiovascular phenotypes are correlated with integrins and tetraspanins. For instance, Cd82 and ITGA9, again, have correlations with blood pressure in mice.Conclusion:ITGA9 is related to blood pressure in both species. KEGG analysis also linked ITGA9 to metabolism and MAPK signaling pathway. This work provides an example of using integrated bioinformatics approaches across different species to identify the connections of structurally and/or functionally related molecules to certain categories of diseases.

Bifurcation in a Simple Model of the Cardiovascular System

2000 ◽  
Vol 39 (02) ◽  
pp. 118-121 ◽  
Author(s):  
S. Akselrod ◽  
S. Eyal
Keyword(s):  
Nonlinear Dynamics ◽  
Blood Pressure ◽  
Heart Rate ◽  
Fixed Point ◽  
Cardiovascular System ◽  
Modified Model ◽  
Mayer Waves ◽  
Sustained Oscillations ◽  
Human Cardiovascular System ◽  
Physiological Values

Abstract:A simple nonlinear beat-to-beat model of the human cardiovascular system has been studied. The model, introduced by DeBoer et al. was a simplified linearized version. We present a modified model which allows to investigate the nonlinear dynamics of the cardiovascular system. We found that an increase in the -sympathetic gain, via a Hopf bifurcation, leads to sustained oscillations both in heart rate and blood pressure variables at about 0.1 Hz (Mayer waves). Similar oscillations were observed when increasing the -sympathetic gain or decreasing the vagal gain. Further changes of the gains, even beyond reasonable physiological values, did not reveal another bifurcation. The dynamics observed were thus either fixed point or limit cycle. Introducing respiration into the model showed entrainment between the respiration frequency and the Mayer waves.

scholarly journals A computational physiology approach to personalized treatment models: the beneficial effects of slow breathing on the human cardiovascular system

2014 ◽  
Vol 307 (7) ◽  
pp. H1073-H1091 ◽  
Author(s):  
Maria Fonoberova ◽  
Igor Mezić ◽  
Jennifer F. Buckman ◽  
Vladimir A. Fonoberov ◽  
Adriana Mezić ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Cardiovascular System ◽  
Empirical Support ◽  
System Level ◽  
Heart Period ◽  
Heart Rate Variability Biofeedback ◽  
Human Cardiovascular System ◽  
Slow Breathing

Heart rate variability biofeedback intervention involves slow breathing at a rate of ∼6 breaths/min (resonance breathing) to maximize respiratory and baroreflex effects on heart period oscillations. This intervention has wide-ranging clinical benefits and is gaining empirical support as an adjunct therapy for biobehavioral disorders, including asthma and depression. Yet, little is known about the system-level cardiovascular changes that occur during resonance breathing or the extent to which individuals differ in cardiovascular benefit. This study used a computational physiology approach to dynamically model the human cardiovascular system at rest and during resonance breathing. Noninvasive measurements of heart period, beat-to-beat systolic and diastolic blood pressure, and respiration period were obtained from 24 healthy young men and women. A model with respiration as input was parameterized to better understand how the cardiovascular processes that control variability in heart period and blood pressure change from rest to resonance breathing. The cost function used in model calibration corresponded to the difference between the experimental data and model outputs. A good match was observed between the data and model outputs (heart period, blood pressure, and corresponding power spectral densities). Significant improvements in several modeled cardiovascular functions (e.g., blood flow to internal organs, sensitivity of the sympathetic component of the baroreflex, ventricular elastance) were observed during resonance breathing. Individual differences in the magnitude and nature of these dynamic responses suggest that computational physiology may be clinically useful for tailoring heart rate variability biofeedback interventions for the needs of individual patients.

scholarly journals Mathematical Modeling of the Antihypertensive Drugs Action

2019 ◽  
Vol 14 (1) ◽  
pp. 233-256
Author(s):  
I.N. Kiselev ◽  
E.O. Kutumova ◽  
A.F. Kolpakova ◽  
G.I. Lifshits ◽  
F.A. Kolpakov
Keyword(s):  
Mathematical Modeling ◽  
Blood Pressure ◽  
Clinical Trials ◽  
Cardiovascular System ◽  
Antihypertensive Drugs ◽  
Mechanisms Of Action ◽  
Virtual Patients ◽  
Blood Pressure Decrease ◽  
Human Cardiovascular System ◽  
Good Agreement

Arterial hypertension is one of the most common diseases of the human cardiovascular system and is characterized by persistent increase in blood pressure. Normalization of blood pressure can be achieved by using antihypertensive drugs with various mechanisms of action. In this work, we investigated a modular mathematical model of the human cardiovascular system created earlier, and complemented it with pharmacodynamic models of five different classes of antihypertensive drugs with such exemplars as aliskiren, losartan, bisoprolol, enalapril and amlodipine. We used clinical trials found in the literature in order to validate the resulting model. Specifically, we generated a population of virtual patients with high blood pressure and modeled their treatment with these antihypertensive drugs. Eventually, the model predicted blood pressure decrease in good agreement with clinical trials. In this way, our model can be further used to optimize the choice of drugs for a particular patient.In silico

scholarly journals Simulating Dynamics of Circulation in the Awake State and Different Stages of Sleep Using Non-autonomous Mathematical Model With Time Delay

2021 ◽  
Vol 11 ◽  
Author(s):  
Anatoly S. Karavaev ◽  
Yurii M. Ishbulatov ◽  
Mikhail D. Prokhorov ◽  
Vladimir I. Ponomarenko ◽  
Anton R. Kiselev ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mathematical Model ◽  
Cardiovascular System ◽  
Healthy Subjects ◽  
Blood Circulation ◽  
Control Loops ◽  
Awake State ◽  
Proposed Model ◽  
Human Cardiovascular System ◽  
First Time

We propose a mathematical model of the human cardiovascular system. The model allows one to simulate the main heart rate, its variability under the influence of the autonomic nervous system, breathing process, and oscillations of blood pressure. For the first time, the model takes into account the activity of the cerebral cortex structures that modulate the autonomic control loops of blood circulation in the awake state and in various stages of sleep. The adequacy of the model is demonstrated by comparing its time series with experimental records of healthy subjects in the SIESTA database. The proposed model can become a useful tool for studying the characteristics of the cardiovascular system dynamics during sleep.

scholarly journals A New Blood Pulsation Simulator Platform Incorporating Cardiovascular Physiology for Evaluating Radial Pulse Waveform

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Tae-Heon Yang ◽  
Jaeuk U. Kim ◽  
Young-Min Kim ◽  
Jeong-Hoi Koo ◽  
Sam-Yong Woo
Keyword(s):  
Blood Pressure ◽  
Cardiovascular System ◽  
Radial Artery ◽  
Pressure Sensors ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Artery Pressure ◽  
Age Dependent ◽  
Radial Artery Pressure ◽  
Human Cardiovascular System

To meet the need for “standard” testing system for wearable blood pressure sensors, this study intends to develop a new radial pulsation simulator that can generate age-dependent reference radial artery pressure waveforms reflecting the physiological characteristics of human cardiovascular system. To closely duplicate a human cardiovascular system, the proposed simulator consists of a left ventricle simulation module, an aorta simulation module, a peripheral resistance simulation module, and a positive/negative pressure control reservoir module. Simulating physiologies of blood pressure, the compliance chamber in the simulator can control arterial stiffness to produce age-dependent pressure waveforms. The augmentation index was used to assess the pressure waveforms generated by the simulator. The test results show that the simulator can generate and control radial pressure waveforms similar to human pulse signals consisting of early systolic pressure, late systolic pressure, and dicrotic notch. Furthermore, the simulator’s left ventricular pressure-volume loop results demonstrate that the simulator exhibits mechanical characteristics of the human cardiovascular system. The proposed device can be effectively used as a “standard” radial artery pressure simulator to calibrate the wearable sensor’s measurement characteristics and to develop more advanced sensors. The simulator is intended to serve as a platform for the development, performance verification, and calibration of wearable blood pressure sensors. It will contribute to the advancement of the wearable blood pressure sensor technology, which enables real-time monitoring of users’ radial artery pressure waveforms and eventually predicting cardiovascular diseases.

A model of human cardiovascular system containing a loop for the autonomic control of mean blood pressure

2017 ◽  
Vol 43 (1) ◽  
pp. 61-70 ◽  
Author(s):  
A. S. Karavaev ◽  
Yu. M. Ishbulatov ◽  
A. R. Kiselev ◽  
V. I. Ponomarenko ◽  
M. D. Prokhorov ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular System ◽  
Autonomic Control ◽  
Mean Blood Pressure ◽  
Human Cardiovascular System

scholarly journals Analysis of microRNA expression in CD133 positive cancer stem‑like cells of human osteosarcoma cell line MG-63

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12115
Author(s):  
Xiong Shu ◽  
Weifeng Liu ◽  
Huiqi Liu ◽  
Hui Qi ◽  
Chengai Wu ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Cell Line ◽  
Signaling Pathway ◽  
Target Genes ◽  
Wnt Signaling Pathway ◽  
Mapk Signaling ◽  
Pcr Analysis ◽  
Pathway Enrichment Analysis ◽  
Osteosarcoma Cell ◽  
Expression Levels

Osteosarcoma (OS) is a primary malignant tumor of bone occurring in young adults. OS stem cells (OSCs) play an important role in the occurrence, growth, metastasis, drug resistance and recurrence of OS. CD133 is an integral membrane glycoprotein, which has been identified as an OSC marker. However, the mechanisms of metastasis, chemoresistance, and progression in CD133(+) OSCs need to be further explored. In this study, we aim to explore differences in miRNA levels between CD133(+) and CD133(−) cells from the MG-63 cell line. We found 20 differentially expressed miRNAs (DEmiRNAs) (16 upregulated and 4 downregulated) in CD133(+) cells compared with CD133(−) cells. Hsa-miR-4485-3p, hsa-miR-4284 and hsa-miR-3656 were the top three upregulated DEmiRNAs, while hsa-miR-487b-3p, hsa-miR-493-5p and hsa-miR-431-5p were the top three downregulated DEmiRNAs. In addition, RT-PCR analysis confirmed that the expression levels of hsa-miR-4284, hsa-miR-4485-3p and hsa-miR-3656 were significantly increased, while the expression levels of hsa-miR-487b-3p, hsa-miR-493-5p, and hsa-miR-431-5p were significantly decreased in CD133(+) cells compared with CD133(−) cells. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that predicted or validated target genes for all 20 DEmiRNAs or the selected 6 DEmiRNAs participated in the “PI3K-Akt signaling pathway,” “Wnt signaling pathway,” “Rap1 signaling pathway,” “Cell cycle” and “MAPK signaling pathway”. Among the selected six DEmiRNAs, miR-4284 was especially interesting. MiR-4284 knockdown significantly reduced the sphere forming capacity of CD133(+) OS cells. The number of invasive CD133(+) OS cells was markedly decreased after miR-4284 knockdown. In addition, miR-4284 knockdown increased the p-β-catenin levels in CD133(+) OS cells. In conclusion, RNA-seq analysis revealed DEmiRNAs between CD133(+) and CD133(−) cells. MiRNAs might play significant roles in the function of OSCs and could serve as targets for OS treatment. MiR-4284 prompted the self-renewal and invasion of OSCs. The function of miR-4284 might be associated with the Wnt signaling pathway.

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