Proinflammatory cytokines and ageing of the cardiovascular-renal system

Smykiewicz, P; Segiet, Agnieszka; Keag, Michelle; Żera, Tymoteusz

doi:10.1016/j.mad.2018.07.006

Cited by 25 publications

(23 citation statements)

References 169 publications

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“…In addition to the stimulation of inflammatory cytokine release, an increased expression of adhesion molecules can be interpreted as an additional sign of inflammatory activation in our study. An enhanced expression of adhesion molecules such as VCAM and ICAM is regarded as a manifestation of endothelial dysfunction accompanied by leukocyte infiltration into the vessel wall and is considered a consequence of chronic exposure to inflammatory cytokines [ 65 , 66 , 67 ]. We have already shown the ability of ECFCs to express adhesion molecules in previous studies [ 63 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

Cyclosporine A and Tacrolimus Induce Functional Impairment and Inflammatory Reactions in Endothelial Progenitor Cells

Meyer

Brodowski

Kaisenberg

et al. 2021

IJMS

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Immunosuppressants are a mandatory therapy for transplant patients to avoid rejection of the transplanted organ by the immune system. However, there are several known side effects, including alterations of the vasculature, which involve a higher occurrence of cardiovascular events. While the effects of the commonly applied immunosuppressive drugs cyclosporine A (CsA) and tacrolimus (Tac) on mature endothelial cells have been addressed in several studies, we focused our research on the unexplored effects of CsA and Tac on endothelial colony-forming cells (ECFCs), a subgroup of endothelial progenitor cells, which play an important role in vascular repair and angiogenesis. We hypothesized that CsA and Tac induce functional defects and activate an inflammatory cascade via NF-κB signaling in ECFCs. ECFCs were incubated with different doses (0.01 µM–10 µM) of CsA or Tac. ECFC function was determined using in vitro models. The expression of inflammatory cytokines and adhesion molecules was explored by quantitative real-time PCR and flow cytometry. NF-κB subunit modification was assessed by immunoblot and immunofluorescence. CsA and Tac significantly impaired ECFC function, including proliferation, migration, and tube formation. TNF-α, IL-6, VCAM, and ICAM mRNA expression, as well as PECAM and VCAM surface expression, were enhanced. Furthermore, CsA and Tac led to NF-κB p65 subunit phosphorylation and nuclear translocation. Pharmacological inhibition of NF-κB by parthenolide diminished CsA- and Tac-mediated proinflammatory effects. The data of functional impairment and activation of inflammatory signals provide new insight into mechanisms associated with CsA and Tac and cardiovascular risk in transplant patients.

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Section: Discussionmentioning

confidence: 99%

Cyclosporine A and Tacrolimus Induce Functional Impairment and Inflammatory Reactions in Endothelial Progenitor Cells

Meyer

Brodowski

Kaisenberg

et al. 2021

IJMS

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“…Expression of proinflammatory cytokines increases throughout the human life span, and this increase is correlated with cardiovascular health (28). Chronic low-grade inflammation, in turn, promotes autonomic imbalance, stimulates remodeling, depresses cardiac function, prompts endothelial dysfunction, and leads to a progression of atherosclerosis and impaired renal function (29).…”

Section: Discussionmentioning

confidence: 99%

Patterns of Multimorbidity in a Population-Based Cohort of Older People: Sociodemographic, Lifestyle, Clinical, and Functional Differences

Marengoni

Roso-Llorach

Vetrano

et al. 2019

The Journals of Gerontology: Series A

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Background:The aim of this study is to identify clusters of older persons based on their multimorbidity patterns and to analyze differences among clusters according to sociodemographic, lifestyle, clinical, and functional characteristics. Methods: We analyzed data from the Swedish National Study on Aging and Care in Kungsholmen on 2,931 participants aged 60 years and older who had at least two chronic diseases. Participants were clustered by the fuzzy c-means cluster algorithm. A disease was considered to be associated with a given cluster when the observed/expected ratio was ≥2 or the exclusivity was ≥25%. Results: Around half of the participants could be classified into five clinically meaningful clusters: respiratory and musculoskeletal diseases (RESP-MSK) 15.7%, eye diseases and cancer (EYE-CANCER) 10.7%, cognitive and sensory impairment (CNS-IMP) 10.6%, heart diseases (HEART) 9.3%, and psychiatric and respiratory diseases (PSY-RESP) 5.4%. Individuals in the CNS-IMP cluster were the oldest, with the worst function and more likely to live in a nursing home; those in the HEART cluster had the highest number of co-occurring diseases and drugs, and they exhibited the highest mean values of serum creatinine and C-reactive protein. The PSY-RESP cluster was associated with higher levels of alcoholism and neuroticism. The other half of the cohort was grouped in an unspecific cluster, which was characterized by gathering the youngest individuals, with the lowest number of co-occurring diseases, and the best functional and cognitive status. Conclusions: The identified multimorbidity patterns provide insight for setting targets for secondary and tertiary preventative interventions and for designing care pathways for multimorbid older people.

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“…The NLRP3 inflammasome can be activated under stress and formed by NLRP3 and procaspase-1 via the adaptor protein ASC2 (22). Moreover, the NLRP3 inflammasome exerts an inflammatory effect through its regulation of the release of proinflammatory cytokines, including IL-1β and IL-18, which contribute to the enhancement of cardiomyocyte dysfunction and lead to ventricular remodeling and HF (23,24). In this study, serum levels of IL-1β and IL-18 were significantly higher in the TAC rats.…”

Section: Discussionmentioning

confidence: 99%

Blockade of β-adrenergic signaling suppresses inflammasome and alleviates cardiac fibrosis

Dang¹,

Zhang²,

Li³

et al. 2020

Ann Transl Med

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Background: Heart failure (HF) is an end-stage syndrome of all structural heart diseases which accompanies the loss of myocardium and cardiac fibrosis. Although the role of inflammasome in cardiac fibrosis has recently been a point of focus, the mechanism of inflammasome activation in HF has not yet been elucidated.Methods: In this study, we investigated the expression of inflammasome proteins in a rat thoracic aorta constriction (TAC) model and cultured cardiac fibroblasts with stimulation of norepinephrine (NE).Results: Our results showed that levels of inflammasome proteins in the myocardial of TAC rats were elevated. By blocking β-adrenergic signaling in the rats, inflammasome activation was suppressed and heart function was improved. The stimulation of cultured cardiac fibroblasts with NE activated inflammasome in vitro, which was abrogated by the inhibition of the calcium channels and reactive oxygen species (ROS). The activation of inflammasome by NE promoted cardiac fibrosis, whereas the inhibition of the calcium channels, ROS, and inflammasome reduced this effect.Conclusions: The present study indicated that activation of inflammasome by β-adrenergic signaling promotes cardiac fibrosis. Therefore, modulation of inflammasome during HF might provide a novel strategy to treat this disease.

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Proinflammatory cytokines and ageing of the cardiovascular-renal system

Cited by 25 publications

References 169 publications

Cyclosporine A and Tacrolimus Induce Functional Impairment and Inflammatory Reactions in Endothelial Progenitor Cells

Cyclosporine A and Tacrolimus Induce Functional Impairment and Inflammatory Reactions in Endothelial Progenitor Cells

Patterns of Multimorbidity in a Population-Based Cohort of Older People: Sociodemographic, Lifestyle, Clinical, and Functional Differences

Blockade of β-adrenergic signaling suppresses inflammasome and alleviates cardiac fibrosis

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