Volume 1 Issue 8, August 2022

Collateral arteries may act as natural bypasses that reduce hypoperfusion after a coronary blockage. 3D imaging of neonatal and adult mouse hearts, plus human fetal and diseased adult hearts, is now used to computationally predict flow within the heart, and understand the cardioprotective role of collateral arteries in vivo.

The replacement of damaged cardiomyocytes by extracellular matrix-producing fibroblasts underpins adverse remodeling in the failing heart. New research finds that MHC class II-dependent fibroblast–CD4⁺ T cell interactions in the myocardium lead to fibroblast activation and exacerbate fibrotic remodeling of the myocardium.

Sepsis-derived S100A8/A9 induces GSDMD-dependent platelet pyroptosis via the TLR4–ROS–NLRP3–caspase 1 pathway, leading to the release of oxidized mitochondrial DNA that contributes to the formation of neutrophil extracellular traps (NETs). NETs in turn release S100A8/A9 and accelerate platelet pyroptosis, forming a positive feedback loop and thereby amplifying the production of proinflammatory cytokines.

In this Review, the authors provide an overview of the pathogenic effects of somatic activating PIK3CA mutations in congenital disorders and discuss how the interplay between genetics, cell identity and the environment explains the onset, progression and severity of these disorders with a special focus on the vasculature.

Goerlich et al. review the history of cardiac allo- and xenotransplants, the progress in immunomodulation to prevent rejection, the regulatory requirements for clinical application and the lessons learned from the first genetically modified pig-to-human heart xenotransplantation.

Using data from the MONICA/KORA registry, Chen et al. show that the risk of heat-related non-fatal myocardial infarction was significantly elevated in patients receiving anti-platelet medication and beta-receptor blockers compared with non-users, and the effect of the medications was stronger in younger patients, with lower prevalence of pre-existing cardiovascular disease, compared with older patients.

Su, Chen et al. show that sepsis-derived S100A8/A9 induces GSDMD-dependent platelet pyroptosis via the TLR4/ROS/NLRP3/caspase 1 pathway, leading to the release of ox-mtDNA contributing to neutrophil extracellular traps (NET) formation. NET in turn release S100A8/A9 and accelerate platelet pyroptosis, forming a positive feedback loop, thereby amplifying the production of proinflammatory cytokines. GSDMD deficiency in platelets or pharmacological inhibition of S100A9 using Paquinimod can break this detrimental feedback loop, thus ameliorating excessive NET-mediated inflammation in mouse models of severe sepsis.

Through a combination of transcriptomic and proteomic profiling of human right ventricle tissue with plasma proteome profiling in a Canadian cohort of patients with pulmonary arterial hypertension (PAH), Bonnet et al. discovered new circulating proteins associated with right ventricular dysfunction in the setting of PAH.

Ngwenyama et al. show that cardiac fibroblasts express MHCII during cardiac inflammation, and are able to process extracellular proteins into small peptides that induce CD4⁺ T cell immune responses. Conditional deletion of MHCII in cardiac fibroblasts ameliorates cardiac remodeling and dysfunction induced by cardiac pressure overload, supporting a central role for cardiac fibroblast MHCII in antigen presentation and in cardiac fibrosis and dysfunction in experimental HF.

Anbazhakan et al. use whole-organ imaging and three-dimensional computational fluid dynamics modeling to define spatial architecture and predict blood flow through collaterals in neonate and adult mouse hearts after injury, and compare their findings to the functionality of collaterals in human adult and fetal hearts.