Circulation Research
Taken together, our data for the first time establish a novel and paradigm-shifting concept that endothelial NOX1 drives systematic metabolic phenotypes, via impairment in skeletal muscle mitochondrial dysfunction with novel genetic signatures. Tissue-specific targeting of endothelial NOX1 and novel candidate genes may prove to be robustly effective in treating obesity and metabolic syndrome.
Aortic aneurysm and dissection (AAD) are life-threatening conditions characterized by progressive aortic dilation and acute aortic complications. Despite advances in surgical and endovascular management, effective pharmacological strategies to prevent AAD expansion and rupture are still lacking. The pathogenesis of AAD is increasingly understood to be driven by profound cellular heterogeneity wit…
Endothelial cells (ECs) line the inner layer of the blood vessels and are subjected to hemodynamic shear stress, the frictional force derived from blood flow, most prominently in arteries 1,2 .Vascular structure influences the intensity and patterns of hemodynamic shear stress.Blood flow through straight, non-branching arteries generates unidirectional laminar shear.Conversely, curved or branchin…
These results reveal a surprising chamber-specific isoform landscape of cardiac sodium currents, which may underlie the right ventricular predominant phenotype of Brugada syndrome. These data highlight non-Na<sub>V</sub>1.5 isoforms as potential mediators of chamber-specific cardiac pathologies and as pharmacological targets.
Acetate is a negative regulator of platelet hyperreactivity and thrombus formation via the Olfr78 receptor, and acetate deficiency contributes to platelet hyperreactivity in hypertension. Lifestyle modifications, particularly high-fiber dietary intervention and acetate supplementation, exhibit potent antithrombotic effects in hypertension.
A novel, light-controllable, bioengineered humanized biatrial tissue model was established and could be used to model different atrial arrhythmias, for drug testing, for disease modeling, and for evaluation of novel therapeutic interventions such as biological pacemaking and optogenetic interventions.
These results uncover an ESCRT-mediated membrane deformation machinery that is essential for shaping cardiomyocyte structure in physiological and disease conditions.
These findings reveal a complex interplay between PI signaling, ion channel trafficking, and compensatory phospho-regulation in AngII-induced cardiac pathology. We establish phosphatidylinositol (3,4,5)-trisphosphate depletion as a critical link between chronic AngII signaling and cardiac dysfunction. The dissociation between persistent cellular remodeling and preserved organ function with PTEN i…
These findings establish pharmacological inhibition of RhoA activation as a viable strategy to mitigate myocardial remodeling in HF and provide a conceptual framework for developing reversible inhibitors against previously undruggable small GTPases.
In this study, we have newly identified the potential value of microRNA-27b-5p and microRNA-497-5p as actionable biomarkers of the profibrotic response to IL-11 in the heart. Future studies should validate the translational potential of the microRNAs as new clinical biomarkers and therapeutic targets.
RHOT proteins bind mitochondria to contractile muscle fiber proteins and are required for mitochondrial positioning in cardiomyocytes during development. Our study links mitochondrial motility and local ATP production to structural and functional maturation of the heart.
This study demonstrates an unexpected protective role for VEGF-D in promoting lung endothelial barrier integrity and suggests that paracrine signaling from the alveolar fibroblast niche contributes critically to lung capillary homeostasis.
Arterial Endothelial Deletion of Alk1 Causes Severe Nosebleed by Impairing Nasal Smooth Muscle Cells
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