Circulation research
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Circulation research · May 2021
Mechanisms of Cardiovascular Toxicities Associated With Immunotherapies.
Immune-based therapies have revolutionized cancer treatments. Cardiovascular sequelae from these treatments, however, have emerged as critical complications, representing new challenges in cardio-oncology. ⋯ The recognition of immunotherapy-associated cardiovascular side effects has also catapulted new research questions revolving around the interactions between the immune and cardiovascular systems, and the signaling cascades affected by T cell activation, cytokine release, and immune system dysregulation. Here, we review the specific mechanisms of immune activation from immunotherapies and the resulting cardiovascular toxicities associated with immune activation and excess cytokine production.
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Circulation research · Oct 2020
Integrative Genomic Analysis Reveals Four Protein Biomarkers for Platelet Traits.
Mean platelet volume (MPV) and platelet count (PLT) are platelet measures that have been linked to cardiovascular disease (CVD) and mortality risk. Identifying protein biomarkers for these measures may yield insights into CVD mechanisms. ⋯ We identified 4 proteins that are causally linked to PLTs. These proteins may also have roles in the pathogenesis of CVD via a platelet/blood coagulation-based mechanism.
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Circulation research · Aug 2020
Somatic Gain of KRAS Function in the Endothelium Is Sufficient to Cause Vascular Malformations That Require MEK but Not PI3K Signaling.
We previously identified somatic activating mutations in the KRAS (Kirsten rat sarcoma viral oncogene homologue) gene in the endothelium of the majority of human sporadic brain arteriovenous malformations; a disorder characterized by direct connections between arteries and veins. However, whether this genetic abnormality alone is sufficient for lesion formation, as well as how active KRAS signaling contributes to arteriovenous malformations, remains unknown. ⋯ We demonstrate that active KRAS expression in the endothelium is sufficient for brain arteriovenous malformations, even in the setting of uninjured adult vasculature. Furthermore, the finding that KRAS-dependent lesions are reversible in zebrafish suggests that MEK inhibition may represent a promising therapeutic treatment for arteriovenous malformation patients. Graphical Abstract: A graphical abstract is available for this article.