scholarly journals NO/redox disequilibrium in the failing heart and cardiovascular system

2005 ◽  
Vol 115 (3) ◽  
pp. 509-517 ◽  
Author(s):  
Joshua M. Hare ◽  
Jonathan S. Stamler
Keyword(s):  
Cardiovascular System ◽  
Failing Heart ◽  
Redox Disequilibrium

Inflammageing in the cardiovascular system: mechanisms, emerging targets, and novel therapeutic strategies

2020 ◽  
Vol 134 (17) ◽  
pp. 2243-2262
Author(s):  
Danlin Liu ◽  
Gavin Richardson ◽  
Fehmi M. Benli ◽  
Catherine Park ◽  
João V. de Souza ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Cardiovascular Research ◽  
Inflammatory Processes ◽  
Ach Receptors

Abstract In the elderly population, pathological inflammation has been associated with ageing-associated diseases. The term ‘inflammageing’, which was used for the first time by Franceschi and co-workers in 2000, is associated with the chronic, low-grade, subclinical inflammatory processes coupled to biological ageing. The source of these inflammatory processes is debated. The senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammageing. The SASP is characterised by the release of inflammatory cytokines, elevated activation of the NLRP3 inflammasome, altered regulation of acetylcholine (ACh) nicotinic receptors, and abnormal NAD+ metabolism. Therefore, SASP may be ‘druggable’ by small molecule therapeutics targeting those emerging molecular targets. It has been shown that inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and adverse cardiac remodelling. Therefore, the pathomechanism involving SASP activation via the NLRP3 inflammasome; modulation of NLRP3 via α7 nicotinic ACh receptors; and modulation by senolytics targeting other proteins have gained a lot of interest within cardiovascular research and drug development communities. In this review, which offers a unique view from both clinical and preclinical target-based drug discovery perspectives, we have focused on cardiovascular inflammageing and its molecular mechanisms. We have outlined the mechanistic links between inflammageing, SASP, interleukin (IL)-1β, NLRP3 inflammasome, nicotinic ACh receptors, and molecular targets of senolytic drugs in the context of cardiovascular diseases. We have addressed the ‘druggability’ of NLRP3 and nicotinic α7 receptors by small molecules, as these proteins represent novel and exciting targets for therapeutic interventions targeting inflammageing in the cardiovascular system and beyond.

Pathophysiology of the failing heart

2000 ◽  
Vol 57 (5) ◽  
pp. 284-292 ◽  
Author(s):  
Pieske ◽  
Hasenfuß
Keyword(s):  
Failing Heart ◽  
Circulus Vitiosus

Bei Herzinsuffizienz führt häufig eine primäre myokardiale Schädigung zur Aktivierung kompensatorischer Gegenregulationsmechanismen, die unmittelbar zur Progression der Herzinsuffizienz beitragen (Circulus vitiosus). Am Myokard selbst kommt es neben kompensatorischer Hypertrophie zu Dilatation und Gefügeumbau (Remodeling). Darüber hinaus treten Störungen der Endothelfunktion und Veränderungen der Skelettmuskulatur auf. Hinzu kommen spezifische subzelluläre Veränderungen auf der Ebene der Myozyten, die letztendlich zu einer gestörten Funktion der physiologischen Regulationsmechanismen der myokardialen Kontraktilität führen. Störungen des intrazellulären Ca2+-Stoffwechsels beruhen insbesondere auf einer verminderten Ca2+-Wiederaufnahmekapazität des sarkoplasmatischen Retikulums und einer vermehrten Aktivität des sarkolemmalen Na+/Ca2+-Austauschers. In der Konsequenz führt die Abnahme der intrazellulären systolischen Ca2+-Konzentration bei steigender Schlagfrequenz zur verminderten Aktivierung der kontraktilen Proteine und damit zu der beobachteten negativen Kraft-Frequenz-Beziehung. Die verminderte Expression myokardialer beta-Rezeptoren und Störungen im Bereich der Kopplungsproteine führen zu einer reduzierten Stimulierbarkeit der Adenylatzyklase und einer Abnahme des cAMP-Gehaltes der Myozyten. Hierdurch ist am insuffizienten menschlichen Herzen die Phosphorylierung intrazellulärer Funktionsproteine vermindert. Dies führt zu einer weiteren Abnahme der Ca2+-Wiederaufnahme in das sarkoplasmatische Retikulum und möglicherweise zu einer gesteigerten Ca2+-Sensitivität der kontraktilen Proteine. Der Frank-Starling-Mechanismus scheint am isolierten menschlichen Myokard bei Herzinsuffizienz weitgehend erhalten zu sein. Unter physiologischen Bedingungen kommt es zu einem engen Zusammenspiel dieser Regulationsmechanismen. beta-Rezeptor-Stimulation steigert unmittelbar die myokardiale Kontraktionskraft, führt aber auch zur Potenzierung der Kraft-Frequenz-Beziehung und möglicherweise zu einer Abschwächung der Ca2+-Ansprechbarkeit der kontraktilen Proteine und damit zu einer verminderten Wirksamkeit des Frank-Starling-Mechanismus. Eine Abschwächung der beta-adrenergen Stimulierbarkeit des Myokards kann deshalb zu einer weiteren Verschlechterung der Kraft-Frequenz-Beziehung führen. Inwiefern vasoaktive Peptide (Endothelin, Angiotensin) in diese Regulationsmechanismen bei Herzfrequenz eingreifen, ist derzeit offen.

Electroporation-mediated delivery of functional genes – a promising approach for non-viral-based gene therapy of the failing heart

2010 ◽  
Vol 58 (S 01) ◽  
Author(s):  
S Eigeldinger-Berthou ◽  
P Buntschu ◽  
A Frobert ◽  
S Cook ◽  
MN Giraud ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Functional Genes ◽  
Failing Heart

Long term in vivo reactions to PTFE and polyester in the cardiovascular system - what will be the fate of septal defect occlusion devices?

2014 ◽  
Vol 62 (S 01) ◽  
Author(s):  
M. Sigler ◽  
S. Huell ◽  
R. Foth ◽  
W. Ruschewski ◽  
T. Tirilomis ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Septal Defect

Radiation exposure of patients undergoing nuclear medicine procedures in Germany between 1996 and 2000

2005 ◽  
Vol 44 (05) ◽  
pp. 119-130 ◽  
Author(s):  
P. Schnell-Inderst ◽  
D. Noßke ◽  
M. Weiss ◽  
A. Stamm-Meyer ◽  
G. Brix ◽  
...  
Keyword(s):  
Nuclear Medicine ◽  
Cardiovascular System ◽  
Effective Dose ◽  
Current Status ◽  
Annual Number ◽  
Statistical Parameters ◽  
Public Health Information ◽  
Nuclear Medicine Procedures ◽  
And Gender ◽  
Icrp Publication

Summary:The aim of this study was to estimate both the frequency and effective dose of nuclear medicine procedures performed in Germany between 1996 and 2000 for different subgroups of patients. Methods: Electronically archived data from 14 hospitals and 10 private practices were restored and statistically analyzed. The effective dose per examination was calculated according to ICRP publication 80 using the tissue weighting factors given in ICRP publication 60. Based on the data collected, statistical parameters were computed to characterize the frequency and effective dose of the various nuclear medicine procedures. Results: In total, 604,771 nuclear medicine procedures performed in 433,709 patients were analyzed. On average, 1.4 examinations were carried out per patient and year. The median effective dose was 1.7 [5.-95. percentile; mean: 0.4–8.5; 2.9] mSv per examination and 2.3 [0.5–11.2; 3.5] mSv per patient. Interestingly, the mean effective dose per examination, but not the number of examinations per year increased with the age of the patients. Most frequent were examinations of the thyroid (36.7%), the skeleton (27.1%) and the cardiovascular system (11.1%), which were associated with a median effective dose of 0.5 [0.5–1.1; 0.7] mSv, 3.4 [2.9–5.1; 3.6] mSv and 7.3 [3.2–21.0; 9.5] mSv, respectively. Over the five-year period examined, the total annual number of PET procedures (222.3%) as well as of examinations of thyroid (24.5%), skeleton (17.9%), and the cardiovascular system (14.9%) increased markedly, whereas a decrease was observed for brain (-39.3%), lung (-20.2%) and renal (-15.0%) scans. Conclusion: The age- and gender-specific data presented in this study provide detailed public health information on both the current status and recent trends in the practice of diagnostic nuclear medicine examinations.

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.

The MDP – A newly developed LVAD for partial unloading of the failing heart

2004 ◽  
Vol 52 (S 1) ◽  
Author(s):  
L Demircan ◽  
S Christiansen ◽  
S Rex ◽  
G Langebartels ◽  
N Kuruc ◽  
...  
Keyword(s):  
Failing Heart
Sign in / Sign up

Export Citation Format

Share Document