Volume 99 Issue 3, March 2019

This study characterizes Notch expression and activity, comparing normal blood vessels with atherosclerotic lesions. Smooth muscle cells derived from these sources were used for signaling studies to clarify Notch activity in the diseased state. Proteomic analysis of explanted cells identified differentially expressed proteins in cells from patients with cardiovascular disease.

This study shows that the transcription factor ZBTB46 is expressed in arterial endothelial cells, is regulated by shear stress and cell confluence. ZBTB46 inhibits endothelial cell proliferation through regulation of cell cycle genes, culminating in G0/G1 arrest, and decreased tube formation in an in vitro model of angiogenesis.

Cerebral cavernous malformations (CCMs) are clusters of dilated capillaries affecting around 0.5% of the population. The authors analyzed the phenotypic characteristics of chronic and acute murine models of CCM. The acute model harbored higher lesion burden while the chronic model showed more inflammation and lesional iron deposition.

Osteopontin is a critical mediator of post-ischemic neovascularization. Humans express three primary OPN isoforms: OPNa, OPNb, and OPNc. This study demonstrates that OPN isoforms differentially promote functional post-ischemic arteriogenesis by promoting increased macrophage migration and macrophage accumulation and survival. Future studies will determine the molecular mechanisms underlying these divergent effects.

The authors demonstrate that the gut microbe-derived metabolite trimethylamine N-oxide (TMAO) induces cardiac hypertrophy and fibrosis via TGF-β1/Smad3 signaling, suggesting that inhibition of gut microbes or generation of TMAO may become a potential target for the prevention and treatment of cardiac hypertrophy.

In this study, the authors found that interferon-γ mediates the protective effects of soluble receptor for advanced glycation end-product (SRAGE) on myocardial ischemia/reperfusion (MI/R) injuries in heart, which might be associated with the increasing expression of proteasome β5i. In addition, the increased β5i in cardiomyocytes promoted the p53 degradation which contributed to the anti-apoptosis effects of sRAGE in MI/R injuries.

Human ischemic cardiomyopathy is defined by DNA hypermethylation, methyltransferase EZH2 induction, and transcription factor KLF15 suppression. Together these changes may mediate a gene expression pattern reflecting decreased oxidative phosphorylation and increased cellular remodeling. This study therefore identifies a novel mechanism through which coronary heart disease may be regulated.

This study was designed to investigate the role of polymerase delta interacting protein 2 (Poldip2) in vascular smooth muscle proliferation and neointimal formation. Neointimal formation and proliferating cell nuclear antigen expression were inhibited in Poldip2+/- mice, in part due to induction of the cell cycle inhibitor p21.

Using a novel slingshot 1 phosphatase (SSH1) knock-out mouse model, the authors demonstrate that loss of the actin-binding protein potentiates angiotensin II-induced medial thickening and fibrosis due to altered TGFβ1 signaling, resulting in increased expression of fibronectin and osteopontin.

A poorly developed placental capillary network is associated with early onset fetal growth restriction (FGR) and pre-eclampsia (PE). First trimester placental endothelial cells from pregnancies at increased risk of developing early onset FGR/PE were more sensitive to apoptotic stimuli and this was functionally linked to the synthesis of NO. This may contribute to the poor placental vascular development seen in ongoing pregnancies.

Systemic inflammation generates oxidized high-density lipoprotein (oxHDL) inducing endothelial malfunction mediated by the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). OxHDL interacts with LOX-1 and increases LOX-1 levels to the plasma membrane through the NOX-2/ROS/NF-κB pathway. Oxidative stress is able to induce LOX-1 expression in absence of oxHDL. Also, oxHDL induces TNF-α expression increase, which induces LOX-1 expression.

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