{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:51:49Z","timestamp":1784335909028,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T00:00:00Z","timestamp":1673049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["17PRE33410986"],"award-info":[{"award-number":["17PRE33410986"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["20POST35050017"],"award-info":[{"award-number":["20POST35050017"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Microvascular dysfunction predicts adverse cardiovascular events despite absence of large vessel disease. A shift in the mediator of flow\u2010mediated dilatation (FMD) from nitric oxide (NO) to mitochondrial\u2010derived hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) occurs in arterioles from patients with coronary artery disease (CAD). The underlying mechanisms governing this shift are not completely defined. Lipid phosphate phosphatase 3 (LPP3) is a transmembrane protein that dephosphorylates lysophosphatidic acid, a bioactive lipid, causing a receptor\u2010mediated increase in reactive oxygen species. A single nucleotide loss\u2010of\u2010function polymorphism in the gene coding for LPP3 (rs17114036) is associated with elevated risk for CAD, independent of traditional risk factors. LPP3 is suppressed by miR\u201092a, which is elevated in the circulation of patients with CAD. Repression of LPP3 increases vascular inflammation and atherosclerosis in animal models. We investigated the role of LPP3 and miR\u201092a as a mechanism for microvascular dysfunction in CAD. We hypothesized that modulation of LPP3 is critically involved in the disease\u2010associated shift in mediator of FMD. LPP3 protein expression was reduced in left ventricle tissue from CAD relative to non\u2010CAD patients (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.004), with mRNA expression unchanged (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.96). Reducing LPP3 expression (non\u2010CAD) caused a shift from NO to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> (% maximal dilatation: Control 78.1\u00a0\u00b1\u00a011.4% <jats:italic>vs<\/jats:italic>. Peg\u2010Cat 30.0\u00a0\u00b1\u00a011.2%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). miR\u201092a is elevated in CAD arterioles (fold change: 1.9\u00a0\u00b1\u00a00.01 <jats:italic>P<\/jats:italic>\u00a0=\u00a00.04), while inhibition of miR\u201092a restored NO\u2010mediated FMD (CAD), and enhancing miR\u201092a expression (non\u2010CAD) elicited H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010mediated dilatation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). Our data suggests LPP3 is crucial in the disease\u2010associated switch in the mediator of FMD.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15388-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Lipid phosphate phosphatase 3 (LPP3) expression is reduced in heart tissue\u00a0patients with coronary artery disease (CAD).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Loss of LPP3 in CAD is associated with an increase in the LPP3 inhibitor, miR\u201092a.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Inhibition of LPP3 in the microvasculature of healthy patients mimics the CAD flow\u2010mediated dilatation (FMD) phenotype.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Inhibition of miR\u201092a restores nitric oxide\u2010mediated FMD in the microvasculature of CAD patients.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp283923","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T06:15:07Z","timestamp":1672208107000},"page":"469-481","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Lipid phosphate phosphatase 3 maintains NO\u2010mediated flow\u2010mediated dilatation in human adipose resistance arterioles"],"prefix":"10.1113","volume":"601","author":[{"given":"Dawid S.","family":"Chabowski","sequence":"first","affiliation":[{"name":"Department of Medicine Division of Cardiology Medical College of Wisconsin  Milwaukee WI USA"},{"name":"Cardiovascular Center, Medical College of Wisconsin  Milwaukee WI 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