ABSTRACT
INTRODUCTION: Immune checkpoint inhibitors (ICI) have led to improved survival in patients with a number of different tumor types. The ICI agent nivolumab induces anti-tumor immune responses by inhibiting the programmed cell death 1 protein, but side effects include cardiac immune-related adverse events (irAE) such as myocarditis.¹ The association of nivolumab with atherosclerotic disease has been rarely reported. CASE PRESENTATION: A 62-year-old man with metastatic melanoma and recent myocardial infarction (MI) presented with recurrent MI after having undergone several cycles of nivolumab therapy. Repeat cardiac catheterization revealed rapidly progressive in-stent restenosis and diffuse coronary artery disease (CAD) requiring bypass surgery and warranting cessation of nivolumab therapy. CONCLUSION: Nivolumab has been linked with dysregulation of immune responses including enhanced T cell activity, which is implicated in CAD. The timing of nivolumab therapy and presentation with non ST elevation myocardial infarction in this patient suggests a serious T cell-driven medication adverse effect. Therefore, close monitoring for atherosclerotic disease progression is warranted in patients on immunotherapy.
Subject(s)
Acute Coronary Syndrome , Melanoma , Acute Coronary Syndrome/chemically induced , Humans , Immune Checkpoint Inhibitors , Male , Melanoma/drug therapy , Middle Aged , Nivolumab/adverse effects , Programmed Cell Death 1 Receptor/therapeutic useABSTRACT
Saphenous vein graft interventions compose a small but important subset of percutaneous coronary revascularization. Because of their unique biology, percutaneous angioplasty and stenting require tailored patient and lesion selection and modification of intervention technique to optimize outcomes. The use of embolic protection and appropriate adjunctive pharmacology can help minimize periprocedural complications, such as the no-reflow phenomenon. Recommendations for best practice in saphenous vein graft interventions continue to evolve with emerging research and therapy.
Subject(s)
Graft Occlusion, Vascular/prevention & control , Percutaneous Coronary Intervention/methods , Saphenous Vein/transplantation , Angioplasty, Balloon, Coronary , Embolism/prevention & control , Graft Occlusion, Vascular/therapy , Humans , StentsSubject(s)
Aortic Rupture/etiology , Aortic Valve Insufficiency/etiology , Aortic Valve Stenosis/etiology , Coronary Stenosis/etiology , Aortic Rupture/diagnostic imaging , Aortic Rupture/surgery , Aortic Valve Insufficiency/diagnostic imaging , Aortic Valve Insufficiency/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/surgery , Diagnosis, Differential , Humans , Male , Middle Aged , Treatment Outcome , UltrasonographyABSTRACT
Sterol regulatory element-binding proteins (SREBPs) are a subfamily of basic helix-loop-helix-leucine zipper proteins that regulate lipid metabolism. We show novel evidence of the in vivo occurrence and subnuclear spatial localization of both exogenously expressed SREBP-1a and -2 homodimers and heterodimers obtained by two-photon imaging and spectroscopy fluorescence resonance energy transfer. SREBP-1a homodimers localize diffusely in the nucleus, whereas SREBP-2 homodimers and the SREBP-1a/SREBP-2 heterodimer localize predominantly to nuclear speckles or foci, with some cells showing a diffuse pattern. We also used tethered SREBP dimers to demonstrate that both homo- and heterodimeric SREBPs activate transcription in vivo. Ultrastructural analysis revealed that the punctate foci containing SREBP-2 are electron-dense nuclear bodies, similar or identical to structures containing the promyelocyte (PML) protein. Immunofluorescence studies suggest that a dynamic interplay exists between PML, as well as another component of the PML-containing nuclear body, SUMO-1, and SREBP-2 within these nuclear structures. These findings provide new insight into the overall process of transcriptional activation mediated by the SREBP family.