Volume 1 Issue 6, June 2022

A prospective observational case-report study now shows that thalidomide can be a well-tolerated, efficacious treatment for complications such as pain, bleeding and ulceration from extracranial arteriovenous malformation.

Clonal hematopoiesis is a risk factor for hematological cancers, cardiovascular diseases and death. Two papers now use new experimental and mathematical tools to quantify changes in the clonal composition of human blood over time, and the results have implications for the risk of cardiovascular diseases.

Blood vessels are thought to form either by de novo vasculogenesis or by angiogenesis from pre-existing blood vessels. Research now finds that anal fin blood vessels form by endothelial transdifferentiation from lymphatic vessels.

Rupture or dissection of the aorta is often fatal. Tcheandjieu and colleagues now identify key pathways underlying aortic dilatation, a common prelude to acute aortic events, and assess the utility of a polygenic risk score to identify those at highest risk of aortic death in whom prophylactic surgical repair may be beneficial.

Elucidation of the mechanisms that drive tumor resistance to anti-angiogenic therapies is expected to improve treatment options. This report shows that endothelial apelin signaling promotes the migration of distant venous endothelial cells toward the tumor progenitor cell niche to support vessel expansion and sustain a normoxic microenvironment, and that it does so independently of vascular endothelial growth factor A.

Fibroblast growth factor homologous factors (FHFs) are an auxiliary subunit of the cardiac voltage-gated sodium channel. We found that FHFs can inhibit the arrhythmogenic late sodium current (I_Na,L) in an isoform-specific manner, and engineered an FHF-based cell-penetrating peptide that acts as an inhibitor of I_Na,L and opens avenues for developing future therapeutics.

Using a quantitative statistical approach, we created a 3D atlas of embryonic cardiac morphogenesis from a collection of mouse specimens. The atlas includes the average shape of tissue geometry over time and its range of variability, and it enabled us to identify the onset of cardiac left–right asymmetry.

In a prospective experimental observational study of 18 individuals with severe, recurrent extracranial arteriovenous malformations, thalidomide was effective in reducing pain, healing ulceration, stopping bleeding and resolving cardiac failure.

Libby and Tokgözoğlu discuss the management of atherogenic lipoproteins, notably low-density lipoprotein, with an emphasis on the role of strategies that target PCSK9.

Boon et al. show that thalidomide appears to be efficacious in the management of chronic pain, bleeding and ulceration in 18 patients with severely symptomatic arteriovenous malformations refractory to conventional therapies.

Hansmann et al. show that serial intravascular infusions of conditioned media produced by allogenic umbilical cord mesenchymal stem cells markedly improved the clinical features of a young child with severe pulmonary arterial hypertension. The multi-omic approach analyzing the transcriptome and the proteome of these stem cells isolated from four donors provides initial insight into their beneficial paracrine function.

Yu et al. show that Piezo1 is the stretch-activated mechanosensor that provides the calcium source to activate TRPM4 and the downstream CaMKII-HDAC4-MEF2 pathway, a key mediator in the cardiomyocytes’ hypertrophic response in pressure overload models.