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http://dx.doi.org/10.1002/ajh.26863 | DOI Listing |
Background: Hereditary hemorrhagic telangiectasia (HHT) is an inherited vascular disorder characterized by arteriovenous malformations (AVMs). Loss-of-function mutations in Activin receptor-like kinase 1 (ALK1) cause type 2 HHT and knockout (KO) mice develop AVMs due to overactivation of VEGFR2/PI3K/AKT signaling pathways. However, the full spectrum of signaling alterations in mutants remains unknown and means to combat AVM formation in patients are yet to be developed.
View Article and Find Full Text PDFEur Heart J
November 2024
Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Am J Hematol
January 2025
Department of Molecular Medicine and Medical Biotechnologies, "Federico II" University of Naples, Naples, Italy.
PIEZO1 encodes a mechanoreceptor, a cation channel activated by mechanical stimuli. Gain-of-function (GoF) variants in PIEZO1 cause dehydrated hereditary stomatocytosis (DHS), or xerocytosis, a pleiotropic syndrome characterized by anemia and iron overload. DHS patients develop hepatic iron overload independent of the degree of anemia and transfusion regimen.
View Article and Find Full Text PDFPNAS Nexus
November 2024
Department of Biomedical Engineering, University of California, Irvine, Irvine 92697, USA.
Macrophages in the vascular wall ingest and clear lipids, but abundant lipid accumulation leads to foam cell formation and atherosclerosis, a pathological condition often characterized by tissue stiffening. While the role of biochemical stimuli in the modulation of macrophage function is well studied, the role of biophysical cues and the molecules involved in mechanosensation are less well understood. Here, we use genetic and pharmacological tools to show extracellular oxidized low-density lipoproteins (oxLDLs) stimulate Ca signaling through activation of the mechanically gated ion channel Piezo1.
View Article and Find Full Text PDFBone
January 2025
Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address:
Mechanical loading is essential for bone growth and homeostasis, with osteocytes considered the primary mechanosensors. Deleting the mechanosensitive ion channel Piezo1 from Dmp1-Cre-targeted cells, which include both osteoblasts and osteocytes, resulted in reduced bone mass and impaired skeletal responses to mechanical stimuli. To specifically isolate Piezo1's role in osteocytes, we used Sost-Cre mice to generate mice with Piezo1 deletion exclusively in mature osteocytes.
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