Autophagy in cardiac myxoma: An important puzzle piece in understanding its inflammatory environment.

Background: Cardiac myxomas are rare, predominantly sporadic tumors that can cause heart failure and systematic inflammatory symptoms, and increase the risk of emboli. Their pathophysiology remains poorly understood, but intra-tumoral inflammation and senescence seem to be implicated in it. One of the principal cellular mechanisms implicated in tumor progression is autophagy, largely unknown in myxomas.

Senescence, immune microenvironment, and vascularization in cardiac myxomas.

Aims: Cardiac myxomas are rare tumors of incompletely elucidated pathogenesis. The aim of this study is to explore the possible presence of a senescence phenotype in cardiac myxomas, associated with an inflammatory and vasculogenic tumor microenvironment.

Methods And Results: This is a retrospective study of 29 cardiac myxomas with immunohistochemical detection of various inflammatory, vascular, and senescence markers.

CaM kinase II regulates cardiac hemoglobin expression through histone phosphorylation upon sympathetic activation.

Sympathetic activation of β-adrenoreceptors (β-AR) represents a hallmark in the development of heart failure (HF). However, little is known about the underlying mechanisms of gene regulation. In human ventricular myocardium from patients with end-stage HF, we found high levels of phosphorylated histone 3 at serine-28 (H3S28p).

A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway.

The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP).

Effect of preculture and loading on expression of matrix molecules, matrix metalloproteinases, and cytokines by expanded osteoarthritic chondrocytes.

Objective: One of the pathologic changes that occurs during osteoarthritis (OA) is the degeneration of the pericellular matrix (PCM). Since the PCM is likely to be involved in mechanotransduction, this study was undertaken to investigate the effects of PCM-like matrix accumulation in zonal OA chondrocytes and their influence on chondrocyte response to compression.

Methods: Superficial and middle/deep zone chondrocytes from macroscopically normal cartilage of OA knees were expanded and encapsulated in alginate gels.