{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:11:25Z","timestamp":1793056285645,"version":"4.5.0"},"reference-count":206,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,15]]},"abstract":"<jats:p>\n                    Molecular characterization of vascular anomalies has revealed that affected endothelial cells (ECs) harbor gain-of-function (GOF) mutations in the gene encoding the catalytic \u03b1 subunit of PI3K\u03b1 (\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    ). These\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    mutations are known to cause solid cancers when occurring in other tissues.\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    -related vascular anomalies, or \u201cPIKopathies,\u201d range from simple, i.e., restricted to a particular form of malformation, to complex, i.e., presenting with a range of hyperplasia phenotypes, including the\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    -related overgrowth spectrum. Interestingly, development of PIKopathies is affected by fluid shear stress (FSS), a physiological stimulus caused by blood or lymph flow. These findings implicate PI3K in mediating physiological EC responses to FSS conditions characteristic of lymphatic and capillary vessel beds. Consistent with this hypothesis, increased PI3K signaling also contributes to cerebral cavernous malformations, a vascular disorder that affects low-perfused brain venous capillaries. Because the GOF activity of PI3K and its signaling partners are excellent drug targets, understanding\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    \u2019s role in the development of vascular anomalies may inform therapeutic strategies to normalize EC responses in the diseased state. This Review focuses on\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    \u2019s role in mediating EC responses to FSS and discusses current understanding of\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    dysregulation in a range of vascular anomalies that particularly affect low-perfused regions of the vasculature. We also discuss recent surprising findings linking increased PI3K signaling to fast-flow arteriovenous malformations in hereditary hemorrhagic telangiectasias.\n                  <\/jats:p>","DOI":"10.1172\/jci172843","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T14:00:32Z","timestamp":1715695232000},"source":"Crossref","is-referenced-by-count":41,"title":["Shear stress and pathophysiological PI3K involvement in vascular malformations"],"prefix":"10.1172","volume":"134","author":[{"given":"Salim","family":"Abdelilah-Seyfried","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Biology, Potsdam University, Potsdam, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Ola","sequence":"additional","affiliation":[{"name":"Experimental Pharmacology Mannheim, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, 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