Volume 2 Issue 10, October 2023

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that coordinates cellular responses to environmental stimuli. Two recent Nature papers show that endothelial AHR is responsive to dietary micronutrients, triggering a signaling cascade that supports tissue homeostasis and responses to infection.

Reduced expression of smooth muscle α-actin (αSMA), a crucial piece of the vascular smooth muscle cell cytoplasmic contractile apparatus, contributes to these cells’ dysfunction in vascular diseases. αSMA is now shown to localize in the nucleus and bind chromatin-remodeling complexes to regulate smooth muscle contractile gene expression.

Right ventricular failure is a major cause of morbidity and mortality in pulmonary hypertension. Transcriptomic profiling of adaptive and maladaptive right ventricular remodeling in humans adds to our basic knowledge of myocardial remodeling and identifies molecular subgroups and biomarkers.

Inflammatory monocytes and macrophages in the heart express C-C chemokine receptor 2 (CCR2) on their cell surface and contribute to heart failure pathogenesis. This study established the feasibility of imaging CCR2⁺ cells by positron emission tomography in patients with myocardial infarction.

C-C chemokine receptor type 2 (CCR2) is expressed on inflammatory populations of monocytes and macrophages that contribute to heart failure. In this study, Lavine et al. establish the feasibility of CCR2 imaging in patients who have had a myocardial infarction.

Sweat, Cao et al. used different genetic and epigenetic approaches to show that Tbx5 is essential for the maintenance of atrial identity in postnatal cardiomyocytes by binding atrial-specific enhancers and maintaining the atrial-specific chromatin architecture, in a dose-dependent manner.

Eberhardt et al. show that SARS-CoV-2 infects human coronary lesions where it preferentially targets plaque macrophages, triggering plaque inflammation and potentially leading to acute cardiovascular complications and long-term cardiovascular risks in patients with COVID-19.

Khassafi et al. identify molecular subgroups of right ventricular (RV) dysfunction using transcriptomic analysis of RV samples from individuals with compensated RV hypertrophy or decompensated RV failure and two rat models of RV dysfunction. Several extracellular matrix genes found to be deregulated in decompensated RV subgroups were validated at the protein level in two independent cohorts of individuals with pulmonary arterial hypertension, revealing their predictive biomarker potential in maladaptive RV development.

Kwartler et al. show that α-smooth muscle actin functions in the nucleus by associating with chromatin remodeling complexes and the promoters of smooth muscle-specific genes, but this nuclear activity is reduced in ACTA2 p.Arg179 pathogenic variants, resulting in impaired smooth muscle differentiation and increased plasticity.