A Novel Pathway of Platelet Activation in ACS Mediated by LL-37 Immunoglobulin G Autoantibody Immune Complexes.

The cathelicidin antimicrobial peptide LL-37 is a self-antigen in neutrophil extracellular traps that provokes autoantibody responses in autoimmune/autoinflammatory conditions. LL-37 immunoglobulin (Ig) G autoantibody levels were measured in subjects with and without atherosclerotic cardiovascular disease assessed using the coronary artery calcium score, in patients who had a future myocardial infarction and in a cohort of acute coronary syndrome (ACS) patients. LL-37 IgG levels were not associated with coronary artery calcium score, but future myocardial infarction patients had significantly higher LL-37 IgG at baseline.

Impaired tolerance to the autoantigen LL-37 in acute coronary syndrome.

Background: LL-37 is the only member of the cathelicidin family of antimicrobial peptides in humans and is an autoantigen in several autoimmune diseases and in acute coronary syndrome (ACS). In this report, we profiled the specific T cell response to the autoimmune self-antigen LL-37 and investigated the factors modulating the response in peripheral blood mononuclear cells (PBMCs) of healthy subjects and ACS patients.

Methods And Results: The activation induced marker (AIM) assay demonstrated differential T cell profiles characterized by the persistence of CD134 and CD137, markers that impair tolerance and promote immune effector and memory response, in ACS compared to Controls.

Immunization using ApoB-100 peptide-linked nanoparticles reduces atherosclerosis.

Active immunization with the apolipoprotein B-100 (ApoB-100) peptide P210 reduces experimental atherosclerosis. To advance this immunization strategy to future clinical testing, we explored the possibility of delivering P210 as an antigen using nanoparticles, given this approach has been used clinically. We first characterized the responses of T cells to P210 using PBMCs from patients with atherosclerotic cardiovascular disease (ASCVD).

The Role of T Cells Reactive to the Cathelicidin Antimicrobial Peptide LL-37 in Acute Coronary Syndrome and Plaque Calcification.

The human cationic anti-microbial peptide LL-37 is a T cell self-antigen in patients with psoriasis, who have increased risk of cardiovascular events. However, the role of LL-37 as a T cell self-antigen in the context of atherosclerosis remains unclear. The objective of this study was to test for the presence of T cells reactive to LL-37 in patients with acute coronary syndrome (ACS).

Sex as a Determinant of Responses to a Coronary Artery Disease Self-Antigen Identified by Immune-Peptidomics.

A significant body of work implicates the adaptive immune response in atherosclerosis, the main underlying cause of coronary artery disease (CAD), yet specific antigens involved remain to be fully identified. The pathobiology of CAD is influenced by sex with many factors that may be involved in the underlying mechanisms. Given the reported sexual dimorphic nature of immune-inflammatory responses, we investigated the influence of sex on potential CAD self-antigens from acute coronary syndrome (ACS) patients using immune-precipitation of soluble HLA Class-I/peptide complexes and mass spectrometry.

Sex differences in crude mortality rates and predictive value of intensive care unit-based scores when applied to the cardiac intensive care unit.

Background: Limited data exists regarding sex differences in outcome and predictive accuracy of intensive care unit-based scoring systems when applied to cardiac intensive care unit patients.

Methods: We reviewed medical records of patients admitted to cardiac intensive care unit from 1 January 2011-31 December 2016. Sex differences in mortality rates and the performance of intensive care unit-based scoring systems in predicting in-hospital mortality were analyzed.

IL-7R blockade reduces post-myocardial infarction-induced atherosclerotic plaque inflammation in ApoE mice.

Modulating inflammation by targeting IL-1β reduces recurrent athero-thrombotic cardiovascular events without lipid lowering. This presents an opportunity to explore other pathways associated with the IL-1β signaling cascade to modulate the inflammatory response post-myocardial infarction (MI). IL-7 is a mediator of the inflammatory pathway involved in monocyte trafficking into atherosclerotic plaques and levels of IL-7 have been shown to be elevated in patients with acute MI.

Keratin 8 is a potential self-antigen in the coronary artery disease immunopeptidome: A translational approach.

Background: Inflammation is an important risk factor in atherosclerosis, the underlying cause of coronary artery disease (CAD). Unresolved inflammation may result in maladaptive immune responses and lead to immune reactivity to self-antigens. We hypothesized that inflammation in CAD patients would manifest in immune reactivity to self-antigens detectable in soluble HLA-I/peptide complexes in the plasma.

Cancellation of the Cardiac Catheterization Lab After Activation for ST-Segment-Elevation Myocardial Infarction.

Background: Prehospital ECG-based cardiac catheterization laboratory (CCL) activation for ST-segment-elevation myocardial infarction reduces door-to-balloon times, but CCL cancellations (CCL) remain a challenging problem. We examined the reasons for CCL, clinical characteristics, and outcomes of patients presenting as ST-segment-elevation myocardial infarction activations who receive emergent coronary angiography (EA) compared with CCL.

Methods And Results: We reviewed all consecutive CCL activations between January 1, 2012, and December 31, 2014 (n=1332).

Early mobility in frail and non-frail older adults admitted to the cardiovascular intensive care unit.

Purpose: Little is known about the effects of early mobilization in older adults in the Cardiovascular Intensive Care Unit (CICU).

Materials And Methods: We reviewed consecutive patients ≥60 years of age admitted to the CICU at an academic tertiary care center from 2016 to 2017. The level of function (LOF) was assessed prehospital, at CICU admission, and at CICU transfer using a graded scale ranging from LOF 1 (bedbound) to 4 (walk > 50 ft).

Systematic review and directors survey of quality indicators for the cardiovascular intensive care unit.

Background: Quality indicators (QIs) are increasingly used in cardiovascular care as measures of performance but there is currently no consensus on indicators for the cardiovascular intensive care unit (CICU).

Methods: We searched Medline, CINAHL, EMBASE, and COCHRANE databases from inception until October 2016 and websites for organizations involved in quality measurement for QIs relevant to cardiovascular disease in an intensive or critical care setting. We surveyed 14 expert cardiac intensivist-administrators (7 European; 7 North American) on the importance and relevance of each indicator as a measure of CICU care quality using a scale of 1 (=lowest) to 10 (=highest).

Noncardiovascular Disease and Critical Care Delivery in a Contemporary Cardiac and Medical Intensive Care Unit.

Background: Noncardiovascular comorbidities and critical illness are increasing in cardiovascular intensive care units (CICUs). There are limited data comparing critical care delivery, resource utilization, and costs between contemporary CICUs and medical intensive care units (MICUs).

Methods: All CICU (n = 6967; 22 748 patient-days) and MICU (n = 10 892; 39 211 patient-days) admissions to Cedars-Sinai Medical Center, a tertiary care academic medical center, between January 2011 and December 2016 were reviewed.

The cathelicidin protein CRAMP is a potential atherosclerosis self-antigen in ApoE(-/-) mice.

Auto-immunity is believed to contribute to inflammation in atherosclerosis. The antimicrobial peptide LL-37, a fragment of the cathelicidin protein precursor hCAP18, was previously identified as an autoantigen in psoriasis. Given the reported link between psoriasis and coronary artery disease, the biological relevance of the autoantigen to atherosclerosis was tested in vitro using a truncated (t) form of the mouse homolog of hCAP18, CRAMP, on splenocytes from athero-prone ApoE(-/-) mice.

Early Coronary Angiography for Survivors of Out-of-Hospital Cardiac Arrests Without ST Elevation.

There are over 300,000 out-of-hospital cardiac arrests (OOHCA) in the United States each year, and the long-term survival rate is less than 10%. Despite improvements in postarrest management, the greatest drop-off in survival occurs during hospitalization, mostly due to myocardial dysfunction and neurological injury. Coronary artery disease is common in postcardiac arrest patients, with an incidence of approximately 60-80%.

Identification of apoB-100 Peptide-Specific CD8+ T Cells in Atherosclerosis.

Background: T cells are found in atherosclerotic plaques, with evidence supporting a potential role for CD8+ T cells in atherogenesis. Prior studies provide evidence of low-density lipoprotein and apoB-100 reactive T cells, yet specific epitopes relevant to the disease remain to be defined. The current study was undertaken to identify and characterize endogenous, antigen-specific CD8+ T cells in atherosclerosis.

Echo-Doppler determinants of outcomes in patients with unoperated significant mitral regurgitation in current era.

Objective: One-half of patients with severe symptomatic mitral regurgitation (MR) do not undergo surgery due to comorbidities. We evaluated prognosticators of outcomes in patients with unoperated significant MR.

Methods: In this observational study, we retrospectively evaluated medical records of 75 consecutive patients with unoperated significant MR.

ApoB-100-related peptide vaccine protects against angiotensin II-induced aortic aneurysm formation and rupture.

Background: T cells and macrophages are implicated in the pathogenesis of aortic aneurysm (AA) and atherosclerosis. We recently demonstrated that a vaccine using an apoB-100-related peptide p210 reduces atherosclerosis with favorable modulation of CD8+ T cells in apolipoprotein E-deficient (apoE-/-) mice.

Objectives: This study hypothesized that a p210 vaccine could reduce AA formation in the angiotensin II (Ang II)-induced AA model.

Cholesterol lowering modulates T cell function in vivo and in vitro.

Background: The lipid milleu exacerbates the inflammatory response in atherosclerosis but its effect on T cell mediated immune response has not been fully elucidated. We hypothesized that lipid lowering would modulate T cell mediated immune function.

Methods And Results: T cells isolated from human PBMC or splenic T cells from apoE-/- mouse had higher proliferative response to T cell receptor (TCR) ligation in medium supplemented with 10% fetal bovine serum (FBS) compared to medium with 10% delipidated FBS.

CD8(+)CD25(+) T cells reduce atherosclerosis in apoE(-/-) mice.

Background: It is increasingly evident that CD8(+) T cells are involved in atherosclerosis but the specific subtypes have yet to be defined. CD8(+)CD25(+) T cells exert suppressive effects on immune signaling and modulate experimental autoimmune disorders but their role in atherosclerosis remains to be determined. The phenotype and functional role of CD8(+)CD25(+) T cells in experimental atherosclerosis were investigated in this study.

Echocardiography in the use of noninvasive hemodynamic monitoring.

Invasive pulmonary artery catheter measurements are the standard method for assessment of hemodynamic evaluation at the present time. However, this invasive approach is associated with an increase in patient morbidity and without evidence of a reduction in mortality. Doppler echocardiography is a noninvasive method that provides robust data regarding patients' hemodynamic indices.