English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Aims Several strategies based on immune checkpoint inhibitors (ICIs) have been developed or are under investigation for cancer therapy, opening to advantages in cancer outcomes. However, several ICIs-induced side effects emerged in these patients, especially a rare but clinically significant cardiotoxicity with high rate of mortality. We analysed the differential vasculo and cardiotoxicity of Pembrolizumab, Nivolumab and Ipilimumab in preclinical models highlighting on the molecular pathways involved. Methods C57 female mice were treated with Ipilimumab, Pembrolizumab or Nivolumab (15 mg/kg) through intraperitoneal injection for 10 days. Before and after treatments, analysis of fractional shortening, ejection fraction, radial and longitudinal strain was performed through 2D-echocardiography (Vevo 2100, Visual Sonics Fujfilm). Fibrosis, necrosis, hypertrophy and vascular/myocardial NF-kB expression were analysed through Immunohistochemistry (IHC). DAMPs, NLRP3, MyD88, p65/NF-kB and 12 cytokines have been analysed in murine myocardium and in cardiomyocytes co-incubated with hPBMC. Results In preclinical models, treatment with Nivolumab leads to increased vascular and myocardial NF-kB expression without affecting fibrosis unlike Ipilimumab which also increases cardiac collagen production. Pembrolizumab increased myocardial hypertrophy and fibrosis in cardiac tissues with a strong vascular NF-kB expression. All tested ICIs increased DAMPs, NLRP3 inflammasome-IL1β-IL18 axis and only Pembrolizumab increased significantly the MyD88 expression vs. untreated mice. Conclusions In preclinical models, Pembrolizumab exerts the most relevant cardiotoxicity compared to Nivolumab and Ipilimumab, increasing immune infiltration in the myocardium and vascular inflammation. All tested ICIs increased DAMPs, NLRP3/IL-1β and MyD88 expression, leading to pro-inflammatory cytokine storm in heart tissues.

european heart journal supplements

88 Differential cardiotoxicity of immune checkpoint inhibitors involves damps fibronectin-EDA, calgranulin, galectine-3, and associated nlrp3 inflammasome-interleukins pathway in preclinical models