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Diverse mutations in RPL3L, the muscle-specific paralog of the ribosomal protein RPL3, have been associated with severe infantile dilated cardiomyopathy and often fatal heart failure. We show that disease is primarily driven by hotspot RPL3L variants that simultaneously block ribosome biogenesis and induce unproductive splicing of the RPL3 precursor mRNA, thereby preventing any compensatory effects of the ubiquitously expressed RPL3.
Murphy et al. reveal a unifying pathogenetic mechanism according to which diverse mutations in the muscle-specific ribosomal protein RPL3L cause severe neonatal dilated cardiomyopathy, establishing a framework for interpreting the growing spectrum of RPL3L variants.
Defects in elastin trigger hyperproliferation of smooth muscle cells, which leads to arterial and congenital heart diseases. Research now shows that elastin deficiency induces SPHK1 and S1P signaling by EGR1 in SMCs, and inhibitors of SPHK1 or S1PR1 attenuate smooth muscle cell proliferation and mitigate aortic disease.
Saito et al. identify sphingosine kinase 1 as a critical regulator of physiological ductus arteriosus closure and pathological supravalvular aortic stenosis through its role in smooth muscle cell proliferation and propose potential therapeutics.
Correlating the mitochondrial membrane potential with the redox status of endogenous mitochondrial cytochromes in vitro enabled the real-time determination of the mitochondrial membrane potential in an isolated perfused mouse heart. This model was used to provide insights into cardiac ischemia–reperfusion injury.
Most drugs in phase 2 trials fail to reach regulatory approval. By leveraging machine learning to identify connections between different types of data, including genes, diseases, medications, existing drugs and images, a new approach is shown to increase the level of evidence in identifying drug targets for cardiovascular disease.
The transcription factor TBX5 regulates early cardiac progenitor cells and genes that encode essential patterning cues for the correct formation of the interventricular septum and separation of cardiac chambers in mice. Disruption of a compartment boundary at the developing interventricular septum reveals potential mechanisms that might underlie some congenital heart defects.
