Loss of developmentally derived Irf8+ macrophages promotes hyperinnervation and arrhythmia in the adult zebrafish heart.

Recent developments in cardiac macrophage biology have broadened our understanding of the critical functions of macrophages in the heart. As a result, there is further interest in understanding the independent contributions of distinct subsets of macrophage to cardiac development and function. Here, we demonstrate that genetic loss of interferon regulatory factor 8 (Irf8)-positive embryonic-derived macrophages significantly disrupts cardiac conduction, chamber function, and innervation in adult zebrafish.

IL-1β-mediated adaptive reprogramming of endogenous human cardiac fibroblasts to cells with immune features during fibrotic remodeling.

The source and roles of fibroblasts and T-cells during maladaptive remodeling and myocardial fibrosis in the setting of pulmonary arterial hypertension (PAH) have been long debated. We demonstrate, using single-cell mass cytometry, a subpopulation of endogenous human cardiac fibroblasts expressing increased levels of CD4, a helper T-cell marker, in addition to myofibroblast markers distributed in human fibrotic RV tissue, interstitial and perivascular lesions in SUGEN/Hypoxia (SuHx) rats, and fibroblasts labeled with pdgfrα CreERt2/+ in R26R-tdTomato mice. Recombinant IL-1β increases IL-1R, CCR2 receptor expression, modifies the secretome, and differentiates cardiac fibroblasts to form CD68-positive cell clusters.

Long-term statin therapy is associated with severe coronary artery calcification.

Background: Atherosclerosis and consequent risk of cardiovascular events or mortality can be accurately assessed by quantifying coronary artery calcium score (CACS) derived from computed tomography. HMG-CoA-reductase inhibitors (statins) are the primary pharmacotherapy used to reduce cardiovascular events, yet there is growing data that support statin use may increase coronary calcification. We set out to determine the likelihood of severe CACS in the context of chronic statin therapy.

Reconsideration of the Gastroparetic Syndrome.

Purpose Of Review: Gastroparesis is a chronic disorder characterized by a constellation of foregut symptoms, including postprandial nausea, vomiting, distension, epigastric pain, and regurgitation in the absence of gastric outlet obstruction. Despite considerable research over the past decades, there remains to be only nominal understanding of disease classification, diagnostic criteria, pathogenesis, and preferred therapy.

Recent Findings: We critically reassess current approaches for disease identification and stratification, theories of causation, and treatment for gastroparesis.

Right Ventricular Architectural Remodeling and Functional Adaptation in Pulmonary Hypertension.

Background: Global indices of right ventricle (RV) function provide limited insights into mechanisms underlying RV remodeling in pulmonary hypertension (PH). While RV myocardial architectural remodeling has been observed in PH, its effect on RV adaptation is poorly understood.

Methods: Hemodynamic assessments were performed in 2 rodent models of PH.

Macrophage IL-1β promotes arteriogenesis by autocrine STAT3- and NF-κB-mediated transcription of pro-angiogenic VEGF-A.

Peripheral artery disease (PAD) leads to considerable morbidity, yet strategies for therapeutic angiogenesis fall short of being impactful. Inflammatory macrophage subsets play an important role in orchestrating post-developmental angiogenesis, but the underlying mechanisms are unclear. Here, we find that macrophage VEGF-A expression is dependent upon the potent inflammatory cytokine, IL-1β.

Rac GTPase Signaling in Immune-Mediated Mechanisms of Atherosclerosis.

Coronary artery disease caused by atherosclerosis is a major cause of morbidity and mortality around the world. Data from preclinical and clinical studies support the belief that atherosclerosis is an inflammatory disease that is mediated by innate and adaptive immune signaling mechanisms. This review sought to highlight the role of Rac-mediated inflammatory signaling in the mechanisms driving atherosclerotic calcification.

Formative evaluation results of a phase 2 Center of Biomedical Research Excellence (COBRE).

Introduction: Because a primary focus of Centers of Biomedical Research Excellence (COBRE) is the development of junior-level investigators into competent and successful research scientists, evaluation of their skills, mentoring experiences, and usefulness of COBRE services is paramount to the transition of the Center to a self-sustaining, collaborative, multidisciplinary research environment. A formative evaluation, focused on the processes of a COBRE, was undertaken and is presented here.

Methods: Two instruments, one for completion by junior investigators and one for completion by mentors, were developed for the purpose of evaluating this COBRE.

Building Research Capacity in Vascular Biology in Rhode Island.

The CardioPulmonary Vascular Biology Center for Biomedical Research Excellence (CPVB COBRE) was funded in 2013 by the National Institute for General Medical Sciences to establish a collaborative center for research excellence in vascular biology in Rhode Island. The CPVB COBRE has funded successful junior faculty investigators and pilot projects spanning the research spectrum from basic vascular development mechanisms using zebrafish to clinical research on pulmonary hypertension to the effects of mindfulness on hypertension in pregnancy. The Administrative Core has united the group with an active seminar program with visiting experts, a focus on career development, and the use of evaluation to support continuous improvement.

Adaptive and innate immune mechanisms in cardiac fibrosis complicating pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a syndrome diagnosed by increased mean pulmonary artery (PA) pressure and resistance and normal pulmonary capillary wedge pressure. PAH is characterized pathologically by distal pulmonary artery remodeling, increased pulmonary vascular resistance, and plexiform lesions (PLs). Right ventricular fibrosis and hypertrophy, leading to right ventricular failure, are the main determinants of mortality in PAH.

Coronary endothelial dysfunction prevented by small-conductance calcium-activated potassium channel activator in mice and patients with diabetes.

Objective: To investigate coronary endothelial protection of a small-conductance calcium-activated potassium (SK) channel activator against a period of cardioplegic-hypoxia and reoxygenation (CP-H/R) injury in mice and patients with diabetes (DM) and those without diabetes (nondiabetic [ND]).

Methods: Mouse small coronary arteries/heart endothelial cells (MHECs) and human coronary arterial endothelial cells (HCAECs) were dissected from the harvested hearts of mice (n = 16/group) and from discarded right atrial tissue samples of patients with DM and without DM (n = 8/group). The SK current density of MHECs was measured.

Impact of Slice Thickness on the Predictive Value of Lung Cancer Screening Computed Tomography in the Evaluation of Coronary Artery Calcification.

Background Image reconstruction thickness may impact quantitative coronary artery calcium scoring (CACS) from lung cancer screening computed tomography (LCSCT), limiting its application in practice. Methods and Results We evaluated Agatston-based quantitative CACS from 1.25-mm LCSCT and cardiac computed tomography for agreement in 87 patients.

Feminine identity and functional benefits are key factors in women's decision making about upper limb prostheses: a case series.

Purpose: Although the DEKA Arm promises new abilities, it is unclear if women with upper limb amputation are willing to avail themselves of this new technology. The study purpose was to understand key factors and tradeoffs that shape women's attitudes towards the DEKA Arm.

Methods: This case series includes three women with transradial amputation.

Evaluating the Cardiovascular Safety of New Medications for Type 2 Diabetes: Time to Reassess?

The U.S. Food and Drug Administration (FDA) issued a Guidance for Industry in 2008 defining preapproval and postapproval requirements for the demonstration of cardiovascular safety for all new medications developed for glycemic management in type 2 diabetes.

Nutrition and metabolism in hepatocellular carcinoma.

Hepatocellular carcinoma is the fifth most common human cancer worldwide, with an overall 5-year survival in the range of 10%. In addition to the very substantial role of chronic viral hepatitis in causing hepatocellular carcinoma, nutritional status and specific nutritional factors appear to influence disease risk. This is apparent in the increased risk associated with non-alcoholic hepatic cirrhosis occurring in the context of obesity, the metabolic syndrome, and type 2 diabetes.