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Paradoxical dominant negative activity of an immunodeficiency-associated activating variant.
Elife
January 2025
The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, United Kingdom.
encodes three regulatory subunits of class IA phosphoinositide 3-kinase (PI3K), each associating with any of three catalytic subunits, namely p110α, p110β, or p110δ. Constitutional mutations cause diseases with a genotype-phenotype relationship not yet fully explained: heterozygous loss-of-function mutations cause SHORT syndrome, featuring insulin resistance and short stature attributed to reduced p110α function, while heterozygous activating mutations cause immunodeficiency, attributed to p110δ activation and known as APDS2. Surprisingly, APDS2 patients do not show features of p110α hyperactivation, but do commonly have SHORT syndrome-like features, suggesting p110α hypofunction.
View Article and Find Full Text PDFNon-Canonical TERT Activity Initiates Osteogenesis in Calcific Aortic Valve Disease.
Circ Res
January 2025
Division of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA. (R.A.C., C.C.C., R.W., A.C., C.B., C.R., W.J.M., M.J. Bashline, A.P., A.M.P., P.B., M.J. Brown, C.S.H.).
Background: Calcific aortic valve disease is the pathological remodeling of valve leaflets. The initial steps in valve leaflet osteogenic reprogramming are not fully understood. As TERT (telomerase reverse transcriptase) overexpression primes mesenchymal stem cells to differentiate into osteoblasts, we investigated whether TERT contributes to the osteogenic reprogramming of valve interstitial cells.
View Article and Find Full Text PDFDanlian-Tongmai formula improves diabetic vascular calcification by regulating CCN3/NOTCH signal axis to inhibit inflammatory reaction.
Front Pharmacol
January 2025
National Clinical Research Center for TCM Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Background: Vascular calcification (VC) commonly occurs in diabetes and is associated with cardiovascular disease incidence and mortality. Currently, there is no drug treatment for VC. The Danlian-Tongmai formula (DLTM) is a traditional Chinese medicine (TCM) prescription used for diabetic VC (DVC), but its mechanisms of action remain unclear.
View Article and Find Full Text PDFChemerin is a new sex-specific target in aortic stenosis concomitant with diabetes regulated by the aldosterone/mineralocorticoid receptor axis.
Am J Physiol Heart Circ Physiol
January 2025
Cardiovascular Translational Research. Navarrabiomed (Fundación Miguel Servet), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), Pamplona, Spain.
Diabetes mellitus (DM) increases the risk of aortic stenosis (AS) and worsens its pathophysiology in a sex-specific manner. Aldosterone/mineralocorticoid receptor (Aldo/MR) pathway participates in early stages of AS and in other diabetic-related cardiovascular complications. We aim to identify new sex-specific Aldo/MR targets in AS complicated with DM.
View Article and Find Full Text PDFA case of recurrent mass complicated with mitral annular calcification in a patient with systemic lupus erythematosus.
J Cardiol Cases
October 2024
Department of Cardiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Unlabelled: Mitral annular calcification (MAC) is a chronic degenerative process involving the fibrous support structure of the mitral valve. The prevalence of this condition significantly increases with age, and is higher in patients with cardiovascular risk factors or end-stage renal disease. However, patients with systemic lupus erythematosus (SLE) may develop atherosclerosis and MAC at a relatively young age.
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