Volume 2 Issue 2, February 2023

Clonal hematopoiesis of indeterminate potential (CHIP) is a blood disorder that can increase the risk of cardiovascular disease. A new study reveals that CHIP driven by somatic mutations in DNA damage repair genes increases the risk of CVD in humans, and provides mechanistic insights in murine models.

Tissue infiltration of neutrophils is a key event of sterile and pathogen-induced inflammation; however, there is at present no non-invasive tool to visualize neutrophil dynamics in the body. Bouvain et al. develop a neutrophil-specific tracer that enables longitudinal imaging of neutrophil flux across the whole body.

The mechanisms that link altered metabolism and heart failure remain unclear. A new study defines the role of the lysine demethylase KDM8 in preventing the initiation of dilated cardiomyopathy through epigenetic control of homeostatic cardiac metabolism.

We report a new non-invasive approach to track neutrophils in both mice and humans by directing multimodal fluorine-loaded nanotracers equipped with specific binding peptides to neutrophil surface markers to enable background-free readout by in vivo ¹⁹F MRI.

Variants in the alpha kinase 3 (ALPK3) gene cause cardiomyopathy, but we have little understanding of the mechanisms at play. We demonstrate that ALPK3 forms a critical signaling node that links contractile proteins to protein quality control machinery. These findings may open new therapeutic approaches to treat cardiomyopathies.

Depuydt and Schaftenaar et al. profile the T cell clonality in patients with atherosclerosis by performing single-cell T cell receptor sequencing on carotid artery plaques and matched peripheral blood mononuclear cell samples. The analyses showed plaque-specific clonal expansion in effector CD4⁺ T cells, expressing genes indicative of exposure to activating antigens, thus suggesting that atherosclerosis has an autoimmune component driven by autoreactive CD4⁺ T cells.

Bouvain et al. develop fluorine-loaded nanotracers engineered with binding peptides targeting the neutrophil-specific receptor CD177 for specific and non-invasive mapping of murine and human neutrophil dynamics by whole-body MRI.

Zekavat, Matesanz, Viana-Huete et al. show an increased risk of peripheral artery disease and atherosclerosis in different vascular beds in patients with clonal hematopoiesis of indeterminate potential (CHIP) caused by mutations in DNA damage repair genes, such as TP53. Validations in a mouse model support the causal contribution of TP53-mutant CHIP to atherosclerosis.

McNamara et al. show that ALPK3 is an M-band protein required for phosphorylation of sarcomeric proteins and components of the protein quality control apparatus. Further, the autophagy receptor sequestosome-1 requires ALPK3 activity for sarcomeric localization.

Ahmed et al. show that lysine demethylase 8 (Kdm8) maintains the homeostatic cardiac metabolism by repressing Tbx15, thus preventing dilated cardiomyopathy in mice. In humans, KDM8 was downregulated in hearts affected by dilated cardiomyopathy, and higher TBX15 expression correlated with the strongest downregulation of genes encoding mitochondrial proteins.