Endothelial dysfunction as a complication of anti-cancer therapy

Terwoord, Janée D.; Beyer, Andreas; Gutterman, David D.

doi:10.1016/j.pharmthera.2022.108116

Cited by 30 publications

(17 citation statements)

References 166 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our work, we assumed that endothelial dysfunction leading to tissue hypoxia plays a central role in all manifestations in patients after the radical treatment of breast cancer. This assumption has been confirmed by studies indicating damage to the vascular wall by chemotherapeutic agents [ 31 , 32 ], radiation therapy [ 15 , 33 , 34 ] and the direct toxic effect of the tumor [ 35 ]. At the same time, in the acute phase, there was an increased permeability of the vascular wall as a result of endothelial cell apoptosis and, as a result, vascular collagen deposition [ 36 ] and, in the long-term period, arteriosclerosis, which causes tissue ischemia [ 37 ].…”

Section: Discussionmentioning

confidence: 80%

Adhesion Molecules ICAM-1 and PECAM-1 as Potential Biomarkers of Central Nervous System Damage in Women Breast Cancer Survivors

et al. 2022

View full text Add to dashboard Cite

Breast cancer (BC) is the most common tumor in women worldwide with high mortality rates. Surgical methods followed by radio–chemotherapy are used to treat these tumors. Such treatment can lead to various side effects, including neurological complications. The development of a reliable biomarker to predict the onset of CNS complications could improve clinical outcomes. In the current study, ICAM-1 and PECAM-1 serum levels were measured as potential biomarkers in 45 female patients in a long-term follow-up period after breast cancer treatment, and compared to 25 age-matched female healthy volunteers. Serum levels of both biomarkers, ICAM-1 and PECAM-1 were significantly higher in patients after breast cancer treatment and could be associated with cognitive dysfunction, depression, and vestibulocerebellar ataxia. In conclusion, our results provide a first hint that elevated serum levels of ICAM-1 and PECAM-1 could serve as early predictive biomarkers in breast cancer survivors that might help to improve the management of these patients.

show abstract

Section: Discussionmentioning

confidence: 80%

Adhesion Molecules ICAM-1 and PECAM-1 as Potential Biomarkers of Central Nervous System Damage in Women Breast Cancer Survivors

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The concomitant presence of CV risk factors or conditions such as physical inactivity, smoking, obesity, and diabetes may further induce inflammation worsening the prognosis of cancer and cancer survivor patients [30]. Cancer cells secrete VEGF to stimulate tumour vascularization, which increases vascular permeability and may contribute to microcirculation structural remodelling and perivascular fibrosis [31,32].…”

Section: Oncologic Diseasementioning

confidence: 99%

“…VEGF-A, the most important isoform of VEGF, may promote the proliferation, differentiation, and migration of endothelial cells by interacting with the VEGF-A receptor, as well as NO production [331]. Accordingly, VEGF inhibition is associated with reduced NO bioavailability because of the inhibition of eNOS and concomitant increase in vascular ROS [324,332], resulting in MD [31]. Activation of the ET-1 system with increased concentrations of ET-1, nephrotoxicity and impaired natriuresis induces hypertension along with the inhibition of other growth factors, including plateletderived or fibroblast growth factor, c-Kit and FMS-like tyrosine kinase 3 [333].…”

Section: Oncologic Diseasementioning

confidence: 99%

“…MD is also found in extra-cardiac tissues (i.e., brain, retina, and lungs) and clinically manifests as dementia, depression, anxiety, vision loss or pulmonary hypertension [14]. In the same context, MD has been implicated in rheumatic (e.g., skin MD) and oncologic diseases [24][25][26][27][28][29][30][31][32]. With respect to its prognostic value, MD is associated with an increased risk of short-and long-term adverse CV outcomes [33,34].…”

Section: Introduction: Microcirculation In Cardiovascular Diseasementioning

confidence: 99%

See 1 more Smart Citation

The importance of microvascular inflammation in ageing and age-related diseases: a position paper from the ESH working group on small arteries, section of microvascular inflammation

Mengozzi

Ciuceis

Georgiopoulos

et al. 2023

Journal of Hypertension

View full text Add to dashboard Cite

Microcirculation is pervasive and orchestrates a profound regulatory cross-talk with the surrounding tissue and organs. Similarly, it is one of the earliest biological systems targeted by environmental stressors and consequently involved in the development and progression of ageing and age-related disease. Microvascular dysfunction, if not targeted, leads to a steady derangement of the phenotype, which cumulates comorbidities and eventually results in a nonrescuable, very high-cardiovascular risk. Along the broad spectrum of pathologies, both shared and distinct molecular pathways and pathophysiological alteration are involved in the disruption of microvascular homeostasis, all pointing to microvascular inflammation as the putative primary culprit. This position paper explores the presence and the detrimental contribution of microvascular inflammation across the whole spectrum of chronic age-related diseases, which characterise the 21st-century healthcare landscape. The manuscript aims to strongly affirm the centrality of microvascular inflammation by recapitulating the current evidence and providing a clear synoptic view of the whole cardiometabolic derangement. Indeed, there is an urgent need for further mechanistic exploration to identify clear, very early or disease-specific molecular targets to provide an effective therapeutic strategy against the otherwise unstoppable rising prevalence of age-related diseases.

show abstract

“…Indeed, vascular senescence has been identified as a significant contributor to multiple cardiovascular diseases [reviewed in ( Katsuumi et al, 2018 ; Jia et al, 2019 )]. Furthermore, cancer survivors treated with anthracyclines exhibit endothelial dysfunction and vascular damage ( Terwoord et al, 2022 ), which can be partially attributed to endothelial senescence as we recently reviewed ( Abdelgawad et al, 2022b ). Therefore, there is a compelling need for pharmacological strategies that target endothelial senescence to preserve endothelial function and potentially mitigate the related adverse effects in cancer survivors.…”

Section: Introductionmentioning

confidence: 99%

Metformin mitigates SASP secretion and LPS-triggered hyper-inflammation in Doxorubicin-induced senescent endothelial cells

et al. 2023

View full text Add to dashboard Cite

Introduction: Doxorubicin (DOX), a chemotherapeutic drug, induces senescence and increases the secretion of senescence-associated secretory phenotype (SASP) in endothelial cells (ECs), which contributes to DOX-induced inflammaging. Metformin, an anti-diabetic drug, demonstrates senomorphic effects on different models of senescence. However, the effects of metformin on DOX-induced endothelial senescence have not been reported before. Senescent ECs exhibit a hyper-inflammatory response to lipopolysachharide (LPS). Therefore, in our current work, we identified the effects of metformin on DOX-induced endothelial senescence and LPS-induced hyper-inflammation in senescent ECs.Methods: ECs were treated with DOX ± metformin for 24 h followed by 72 h incubation without DOX to establish senescence. Effects of metformin on senescence markers expression, SA-β-gal activity, and SASP secretion were assessed. To delineate the molecular mechanisms, the effects of metformin on major signaling pathways were determined. The effect of LPS ± metformin was determined by stimulating both senescent and non-senescent ECs with LPS for an additional 24 h.Results: Metformin corrected DOX-induced upregulation of senescence markers and decreased the secretion of SASP factors and adhesion molecules. These effects were associated with a significant inhibition of the JNK and NF-κB pathway. A significant hyper-inflammatory response to LPS was observed in DOX-induced senescent ECs compared to non-senescent ECs. Metformin blunted LPS-induced upregulation of pro-inflammatory SASP factors.Conclusion: Our study demonstrates that metformin mitigates DOX-induced endothelial senescence phenotype and ameliorates the hyper-inflammatory response to LPS. These findings suggest that metformin may protect against DOX-induced vascular aging and endothelial dysfunction and ameliorate infection-induced hyper-inflammation in DOX-treated cancer survivors.

show abstract

Endothelial dysfunction as a complication of anti-cancer therapy

Cited by 30 publications

References 166 publications

Adhesion Molecules ICAM-1 and PECAM-1 as Potential Biomarkers of Central Nervous System Damage in Women Breast Cancer Survivors

Adhesion Molecules ICAM-1 and PECAM-1 as Potential Biomarkers of Central Nervous System Damage in Women Breast Cancer Survivors

The importance of microvascular inflammation in ageing and age-related diseases: a position paper from the ESH working group on small arteries, section of microvascular inflammation

Metformin mitigates SASP secretion and LPS-triggered hyper-inflammation in Doxorubicin-induced senescent endothelial cells

Contact Info

Product

Resources

About