{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:04:24Z","timestamp":1791295464076,"version":"4.1.0"},"reference-count":84,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>\n                      Individuals with\n                      <jats:italic toggle=\"yes\">JAK2V617F<\/jats:italic>\n                      -mutant myeloproliferative neoplasms or clonal hematopoiesis of indeterminate potential have a markedly increased risk of cardiovascular disease, yet the mechanisms by which mutant blood cells drive vascular and cardiac dysfunction remain incompletely understood. Although the thrombopoietin receptor MPL is central to hematopoiesis and is expressed in vascular endothelial cells (ECs), its role in JAK2V617F-associated cardiovascular complications is unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We generated chimeric mice with\n                      <jats:italic toggle=\"yes\">JAK2V617F<\/jats:italic>\n                      -mutant blood cells and wild-type endothelium by bone marrow transplantation and challenged them with a high-fat\/high-cholesterol diet to model cardiometabolic stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Mice with\n                      <jats:italic toggle=\"yes\">JAK2V617F<\/jats:italic>\n                      -mutant blood cells developed a distinct cardiovascular phenotype characterized by microvascular disease, increased left ventricular mass, and relatively preserved left ventricular ejection fraction. Histopathologic analysis revealed coronary arteriole stenosis, perivascular fibrosis, reduced microvascular density, and endocardial injury, without evidence of epicardial coronary stenosis or myocardial infarction. Single-cell RNA sequencing revealed activation of inflammatory, stress-response, and endothelial-to-mesenchymal transition gene signatures in ECs, most prominently within the endocardial ECs. Immunohistochemistry identified MPL expression predominantly in endocardial ECs. Thrombopoietin\/MPL signaling was upregulated in endocardial ECs in mice with\n                      <jats:italic toggle=\"yes\">JAK2V617F<\/jats:italic>\n                      -mutant hematopoiesis, and treatment with an anti-MPL neutralizing antibody markedly improved cardiovascular pathology, restored endocardial integrity, and increased coronary microvascular density.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">JAK2V617F<\/jats:italic>\n                      -mutant hematopoiesis induces cardiac microvascular dysfunction under cardiometabolic stress. Endocardial ECs play a critical role in this pathological process, and endocardial MPL signaling constitutes a potential targetable pathway in JAK2V617F-associated cardiovascular disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.126.325061","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:00:26Z","timestamp":1788426026000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting Thrombopoietin\/MPL Signaling to Mitigate JAK2V617F-Driven Cardiac Microvascular Disease"],"prefix":"10.1161","author":[{"given":"Xiaoxi","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Medicine, Stony Brook School of Medicine, NY (X.Y., K.M., X.S., F.Z., H. 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