Interleukin-1β Drives Disease Progression in Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a genetic form of heart failure that affects 1 in 5000 people globally and is caused by mutations in cardiac desmosomal proteins including , and Individuals with ACM suffer from ventricular arrhythmias, sudden cardiac death, and heart failure. There are few effective treatments and heart transplantation remains the best option for many affected individuals. Here we performed single nucleus RNA sequencing (snRNAseq) and spatial transcriptomics on myocardial samples from patients with ACM and control donors.

Review of Interleukin-6 and Cardiopulmonary Bypass-Related End-Organ Injury Along With the Potential for Mitigation With Tocilizumab.

Cardiopulmonary bypass (CPB) is essential for the conduct of open-heart procedures. While lifesaving, CPB can be associated with significant end-organ injuries believed to result from inflammatory responses triggered by the extracorporeal surfaces encountering cellular elements in the blood stream. In this review, we discuss the role of interleukin-6 (IL-6) and the potential for Tocilizumab, an anti-IL-6 receptor antibody, in mitigating these effects.

Hypoxia sensing in resident cardiac macrophages regulates monocyte fate specification following ischemic heart injury.

Myocardial infarction initiates cardiac remodeling and is central to heart failure pathogenesis. Following myocardial ischemia-reperfusion injury, monocytes enter the heart and differentiate into diverse subpopulations of macrophages. Here we show that deletion of Hif1α, a hypoxia response transcription factor, in resident cardiac macrophages led to increased remodeling and overrepresentation of macrophages expressing arginase 1 (Arg1).

Visualizing Immune Checkpoint Inhibitors Derived Inflammation in Atherosclerosis.

Background: Immune checkpoint inhibitor (ICI) usage has resulted in immune-related adverse events in patients with cancer, such as accelerated atherosclerosis. Of immune cells involved in atherosclerosis, the role of CCR2+ (CC motif chemokine receptor 2-positive) proinflammatory macrophages is well documented. However, there is no noninvasive approach to determine the changes of these cells in vivo following ICI treatment and explore the underlying mechanisms of immune-related adverse events.

Defining cardiac functional recovery in end-stage heart failure at single-cell resolution.

Recovery of cardiac function is the holy grail of heart failure therapy yet is infrequently observed and remains poorly understood. In this study, we performed single-nucleus RNA sequencing from patients with heart failure who recovered left ventricular systolic function after left ventricular assist device implantation, patients who did not recover and non-diseased donors. We identified cell-specific transcriptional signatures of recovery, most prominently in macrophages and fibroblasts.

Targeting Immune-Fibroblast Crosstalk in Myocardial Infarction and Cardiac Fibrosis.

Inflammation and tissue fibrosis co-exist and are causally linked to organ dysfunction. However, the molecular mechanisms driving immune-fibroblast crosstalk in human cardiac disease remains unexplored and there are currently no therapeutics to target fibrosis. Here, we performed multi-omic single-cell gene expression, epitope mapping, and chromatin accessibility profiling in 38 donors, acutely infarcted, and chronically failing human hearts.

Peripheral blood mononuclear cell tissue factor (F3 gene) transcript levels and circulating extracellular vesicles are elevated in severe coronavirus 2019 (COVID-19) disease.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with excessive coagulation, thrombosis, and mortality.

Objective: To provide insight into mechanisms that contribute to excessive coagulation in coronavirus 2019 (COVID-19) disease.

Patients/methods: Blood from COVID-19 patients was investigated for coagulation-related gene expression and functional activities.

Vascular smooth muscle- and myeloid cell-derived integrin α9β1 does not directly mediate the development of atherosclerosis in mice.

Background And Aims: Sushi, von Willebrand factor type A, EGF pentraxin domain-containing 1 (SVEP1), an extracellular matrix protein, is a human coronary artery disease locus that promotes atherosclerosis. We previously demonstrated that SVEP1 induces vascular smooth muscle cell (VSMC) proliferation and an inflammatory phenotype in the arterial wall to enhance the development of atherosclerotic plaque. The only receptor known to interact with SVEP1 is integrin α9β1, a cell surface receptor that is expressed by VSMCs and myeloid lineage-derived monocytes and macrophages.

Donor Macrophages Modulate Rejection After Heart Transplantation.

Background: Cellular rejection after heart transplantation imparts significant morbidity and mortality. Current immunosuppressive strategies are imperfect, target recipient T cells, and have adverse effects. The innate immune response plays an essential role in the recruitment and activation of T cells.

Derivation of extra-embryonic and intra-embryonic macrophage lineages from human pluripotent stem cells.

Tissue-resident macrophages are increasingly recognized as important determinants of organ homeostasis, tissue repair, remodeling and regeneration. Although the ontogeny and function of tissue-resident macrophages has been identified as distinct from postnatal hematopoiesis, the inability to specify, in vitro, similar populations that recapitulate these developmental waves has limited our ability to study their function and potential for regenerative applications. We took advantage of the concept that tissue-resident macrophages and monocyte-derived macrophages originate from distinct extra-embryonic and definitive hematopoietic lineages to devise a system to generate pure cultures of macrophages that resemble tissue-resident or monocyte-derived subsets.

E-wave asymmetry elucidates diastolic ventricular stiffness-relaxation coupling: model-based prediction with in vivo validation.

Load, chamber stiffness, and relaxation are the three established determinants of global diastolic function (DF). Coupling of systolic stiffness and isovolumic relaxation has been hypothesized; however, diastolic stiffness-relaxation coupling (DSRC) remains unknown. The parametrized diastolic filling (PDF) formalism, a validated DF model incorporates DSRC.

Demonstration of a Longitudinal Medical Education Model (LMEM) Model to Teach Point-of-Care Ultrasound in Resource-Limited Settings.

Short-term medical missions prevail as the most common form of international medical volunteerism, but they are ill-suited for medical education and training local providers in resource-limited settings. The purpose of this study is to evaluate the effectiveness of a longitudinal educational program in training clinicians how to perform point-of-care ultrasound (POCUS) in resource-limited clinics. A retrospective study of a four-month POCUS training program was conducted with clinicians from a rural hospital in Haiti.

Mixed Valvular Disease Following Transcatheter Aortic Valve Replacement: Quantification and Systematic Differentiation Using Clinical Measurements and Image-Based Patient-Specific In Silico Modeling.

Background Mixed valvular disease (MVD), mitral regurgitation (MR) from pre-existing disease in conjunction with paravalvular leak (PVL) following transcatheter aortic valve replacement (TAVR), is one of the most important stimuli for left ventricle (LV) dysfunction, associated with cardiac mortality. Despite the prevalence of MVD, the quantitative understanding of the interplay between pre-existing MVD, PVL, LV, and post-TAVR recovery is meager. Methods and Results We quantified the effects of MVD on valvular-ventricular hemodynamics using an image-based patient-specific computational framework in 72 MVD patients.

CellTagging: combinatorial indexing to simultaneously map lineage and identity at single-cell resolution.

Single-cell technologies are offering unparalleled insight into complex biology, revealing the behavior of rare cell populations that are masked in bulk population analyses. One current limitation of single-cell approaches is that lineage relationships are typically lost as a result of cell processing. We recently established a method, CellTagging, permitting the parallel capture of lineage information and cell identity via a combinatorial cell indexing approach.

Automated Segmentation of Bioresorbable Vascular Scaffold Struts in Intracoronary Optical Coherence Tomography Images.

Bioresorbable vascular scaffolds (BVS), the next step in the continuum of minimally invasive vascular interventions present new opportunities for patients and clinicians but challenges as well. As they are comprised of polymeric materials standard imaging is challenging. This is especially problematic as modalities like optical coherence tomography (OCT) become more prevalent in cardiology.

Multilayer flow modulator enhances vital organ perfusion in patients with type B aortic dissection.

Management of aortic dissections (AD) is still challenging, with no universally approved guideline among possible surgical, endovascular, or medical therapies. Approximately 25% of patients with AD suffer postintervention malperfusion syndrome or hemodynamic instability, with the risk of sudden death if left untreated. Part of the issue is that vascular implants may themselves induce flow disturbances that critically impact vital organs.

Polymeric endovascular strut and lumen detection algorithm for intracoronary optical coherence tomography images.

Polymeric endovascular implants are the next step in minimally invasive vascular interventions. As an alternative to traditional metallic drug-eluting stents, these often-erodible scaffolds present opportunities and challenges for patients and clinicians. Theoretically, as they resorb and are absorbed over time, they obviate the long-term complications of permanent implants, but in the short-term visualization and therefore positioning is problematic.