Multidimensional profiling of human T cells reveals high CD38 expression, marking recent thymic emigrants and age-related naive T cell remodeling.

Thymic involution is a key factor in human immune aging, leading to reduced thymic output and a decline in recent thymic emigrant (RTE) naive T cells in circulation. Currently, the precise definition of human RTEs and their corresponding cell surface markers lacks clarity. Analysis of single-cell RNA-seq/ATAC-seq data distinguished RTEs by the expression of SOX4, IKZF2, and TOX and CD38 protein, whereby surface CD38 expression universally identified CD8 and CD4 RTEs.

Emerging Pathway to a Precision Medicine Approach for Angina With Nonobstructive Coronary Arteries in Women.

Women are disproportionately affected by symptoms of angina with nonobstructive coronary arteries (ANOCA) which is associated with significant mortality and economic impact. Although distinct endotypes of ANOCA have been defined, it is underdiagnosed and is often incompletely characterized when identified. Patients are often unresponsive to traditional therapeutic options, which are typically antianginal, and the current ability to guide treatment modification by specific pathways is limited.

Single-cell profiling of CD11c+ B cells in atherosclerosis.

Circulating CD11c+ B cells, a novel subset of activated B cells, have been linked to autoimmunity and shown to expand with age. Atherosclerosis is an age-associated disease that involves innate and adaptive immune responses to modified self-antigens. Yet, the expression of CD11c on specific B-cell subtypes and its link to atherosclerosis are poorly understood.

The impact of COVID-19 on clinical outcomes among acute myocardial infarction patients undergoing early invasive treatment strategy.

Background: The implications of coronavirus disease 2019 (COVID-19) infection on outcomes after invasive therapeutic strategies among patients presenting with acute myocardial infarction (AMI) are not well studied.

Hypothesis: To assess the outcomes of COVID-19 patients presenting with AMI undergoing an early invasive treatment strategy.

Methods: This study was a cross-sectional, retrospective analysis of the National COVID Cohort Collaborative database including all patients presenting with a recorded diagnosis of AMI (ST-elevation myocardial infarction (MI) and non-ST elevation MI).

Reticulocalbin 2 as a Potential Biomarker and Therapeutic Target for Atherosclerosis.

Vascular inflammation initiated by oxidized lipoproteins drives initiation, progression, and even rupture of atherosclerotic plaques. Yet, to date, no biomarker is directly linked to oxidized lipid-induced vascular inflammation. Reticulocalbin 2 (RCN2) is a key regulator of basal and oxidized lipid-induced cytokine production in arterial wall cells.

Cardiovascular Imaging for Ischemic Heart Disease in Women: Time for a Paradigm Shift.

Heart disease is the leading cause of death among men and women. Women have a unique phenotype of ischemic heart disease with less calcified lesions, more nonobstructive plaques, and a higher prevalence of microvascular disease compared with men, which may explain in part why current risk models to detect obstructive coronary artery disease (CAD) may not work as well in women. This paper summarizes the sex differences in the functional and anatomical assessment of CAD in women presenting with stable chest pain and provides an approach for using multimodality imaging for the evaluation of suspected ischemic heart disease in women in accordance to the recently published American Heart Association/American College of Cardiology guidelines for the evaluation and diagnosis of chest pain.

The "July Effect" in the Cardiac Catheterization Laboratory.

In Interventional Cardiology, the academic year and a new training cycle begin in July. It is unclear if patient outcomes are impacted by the time of year in the training cycle. The National Cardiovascular Data Registry collects outcomes related to percutaneous coronary interventions (PCIs).

B-1b Cells Possess Unique bHLH-Driven P62-Dependent Self-Renewal and Atheroprotection.

Background: B1a and B1b lymphocytes produce IgM that inactivates oxidation-specific epitopes (IgM) on LDL (low-density lipoprotein) and protects against atherosclerosis. Loss of ID3 (inhibitor of differentiation 3) in B cells selectively promotes B1b but not B1a cell numbers, leading to higher IgM production and reduction in atherosclerotic plaque formation. Yet, the mechanism underlying this regulation remains unexplored.

Chemokine Receptor Activation Enhances Memory B Cell Class Switching Linked to IgE Sensitization to Alpha Gal and Cardiovascular Disease.

Recent studies have suggested that IgE sensitization to α-gal is associated with coronary artery disease (CAD). However, the B cell subtype(s) responsible for production of IgE to α-gal and mechanisms mediating this production remain elusive. Single cell multi-omics sequencing, was utilized to phenotype B cells obtained from 60 subjects that had undergone coronary angiography in whom serum IgE was evaluated by ImmunoCAP.

Vasopressors independently associated with mortality in acute myocardial infarction and cardiogenic shock.

Background: Increasing vasopressor dose is associated with increasing mortality in patients presenting with acute myocardial infarction and cardiogenic shock (AMICS). It is unknown whether the use of vasopressors is independently harmful or if their use is secondary to decreasing intrinsic cardiac power output (CPO). Mechanical circulatory support (MCS) devices enhance CPO.

Atherosclerosis Impairs Naive CD4 T-Cell Responses via Disruption of Glycolysis.

Objective: CD4 T cells are important regulators of atherosclerotic progression. The metabolic profile of CD4 T cells controls their signaling and function, but how atherosclerosis affects T-cell metabolism is unknown. Here, we sought to determine the impact of atherosclerosis on CD4 T-cell metabolism and the contribution of such metabolic alterations to atheroprogression.

CD200 Limits Monopoiesis and Monocyte Recruitment in Atherosclerosis.

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Characteristics and outcomes of surgically ineligible patients with multivessel disease treated with percutaneous coronary intervention.

Objectives: In this study we evaluated the clinical characteristics and outcomes of surgically ineligible patients with coronary artery disease (CAD) who underwent multivessel percutaneous coronary intervention (PCI).

Background: Patients with multivessel CAD who are surgically ineligible and undergo PCI are not well represented in large trials.

Methods: Out of 1,061 consecutive patients who underwent a non-emergent PCI for unprotected left main or multivessel CAD at the University of Virginia Medical Center, 137 patients were determined to be surgically ineligible for coronary artery bypass graft (CABG) surgery by a heart team.

Intentional removal of erroneously deployed coronary stents: A case series and review of the literature.

Most reports of stent retrieval involve undeployed, embolized stents. While the retrieval of fully deployed stents has been sporadically reported, most of these were not intentional. The feasibility and safety of intentional retrieval of fully deployed, but erroneously placed stents have not been well described.

Diversification and CXCR4-Dependent Establishment of the Bone Marrow B-1a Cell Pool Governs Atheroprotective IgM Production Linked to Human Coronary Atherosclerosis.

Rationale: B-1 cell-derived natural IgM antibodies against oxidation-specific epitopes on low-density lipoprotein are anti-inflammatory and atheroprotective. Bone marrow (BM) B-1a cells contribute abundantly to IgM production, yet the unique repertoire of IgM antibodies generated by BM B-1a and the factors maintaining the BM B-1a population remain unexplored. CXCR4 (C-X-C motif chemokine receptor 4) has been implicated in human cardiovascular disease and B-cell homeostasis, yet the role of B-1 cell CXCR4 in regulating atheroprotective IgM levels and human cardiovascular disease is unknown.

Human Monocyte Heterogeneity as Revealed by High-Dimensional Mass Cytometry.

Objective- Three distinct human monocyte subsets have been identified based on the surface marker expression of CD14 and CD16. We hypothesized that monocytes were likely more heterogeneous in composition. Approach and Results- We used the high dimensionality of mass cytometry together with the FlowSOM clustering algorithm to accurately identify and define monocyte subsets in blood of healthy human subjects and those with coronary artery disease (CAD).

A monoclonal antibody to assess oxidized cholesteryl esters associated with apoAI and apoB-100 lipoproteins in human plasma.

Atherosclerosis is associated with increased lipid peroxidation, leading to generation of multiple oxidation-specific epitopes (OSEs), contributing to the pathogenesis of atherosclerosis and its clinical manifestation. Oxidized cholesteryl esters (OxCEs) are a major class of OSEs found in human plasma and atherosclerotic tissue. To evaluate OxCEs as a candidate biomarker, we generated a novel mouse monoclonal Ab (mAb) specific to an OxCE modification of proteins.

IgE to the Mammalian Oligosaccharide Galactose-α-1,3-Galactose Is Associated With Increased Atheroma Volume and Plaques With Unstable Characteristics-Brief Report.

Objective: Emerging evidence suggests a link between coronary artery disease and type 2 immunity. We sought to test the hypothesis that IgE sensitization to the mammalian oligosaccharide galactose-α-1,3-galactose (α-Gal)-the target allergen of delayed anaphylaxis to red meat-is associated with coronary artery disease.

Approach And Results: Total IgE and specific IgE to α-Gal were assayed on sera from 118 subjects who presented for cardiac catheterization and underwent intravascular ultrasound.

Outcomes of patients with cardiogenic shock treated with TandemHeart percutaneous ventricular assist device: Importance of support indication and definitive therapies as determinants of prognosis.

Objectives: The objective of this study was to review the characteristics of patients in cardiogenic shock treated with TandemHeart percutaneous ventricular assist device (pVAD) to determine influential predictors of survival.

Background: The TandemHeart pVAD is used in the management of patients with cardiogenic shock resulting from a variety of conditions. Several studies have documented the efficacy of this therapy and outlined its complications.

Apolipoprotein AI prevents regulatory to follicular helper T cell switching during atherosclerosis.

Regulatory T (Treg) cells contribute to the anti-inflammatory response during atherogenesis. Here we show that during atherogenesis Treg cells lose Foxp3 expression and their immunosuppressive function, leading to the conversion of a fraction of these cells into T follicular helper (Tfh) cells. We show that Tfh cells are pro-atherogenic and that their depletion reduces atherosclerosis.