{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T12:38:56Z","timestamp":1772455136325,"version":"3.50.1"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Human genetics have implicated the 5-lipoxygenase enzyme in the pathogenesis of cardiovascular disease, and an inhibitor of the 5-lipoxygenase activating protein (FLAP) is in clinical development for asthma.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Here we determined whether FLAP deletion modifies the response to vascular injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Vascular remodeling was characterized 4 weeks after femoral arterial injury in FLAP knockout mice and wild-type controls. Both neointimal hyperplasia and the intima\/media ratio of the injured artery were significantly reduced in the FLAP knockouts, whereas endothelial integrity was preserved. Lesional myeloid cells were depleted and vascular smooth muscle cell (VSMC) proliferation, as reflected by bromodeoxyuridine incorporation, was markedly attenuated by FLAP deletion. Inflammatory cytokine release from FLAP knockout macrophages was depressed, and their restricted ability to induce VSMC migration ex vivo was rescued with leukotriene B\n              <jats:sup>4<\/jats:sup>\n              . FLAP deletion restrained injury and attenuated upregulation of the extracellular matrix protein, tenascin C, which affords a scaffold for VSMC migration. Correspondingly, the phenotypic modulation of VSMC to a more synthetic phenotype, reflected by morphological change, loss of \u03b1-smooth muscle cell actin, and upregulation of vascular cell adhesion molecule-1 was also suppressed in FLAP knockout mice. Transplantation of FLAP-replete myeloid cells rescued the proliferative response to vascular injury.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Expression of lesional FLAP in myeloid cells promotes leukotriene B\n              <jats:sub>4<\/jats:sub>\n              -dependent VSMC phenotypic modulation, intimal migration, and proliferation.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.112.300755","type":"journal-article","created":{"date-parts":[[2012,12,19]],"date-time":"2012-12-19T04:42:24Z","timestamp":1355892144000},"page":"432-440","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Myeloid Cell 5-Lipoxygenase Activating Protein Modulates the Response to Vascular Injury"],"prefix":"10.1161","volume":"112","author":[{"given":"Zhou","family":"Yu","sequence":"first","affiliation":[{"name":"From the The Institute for Translational Medicine and Therapeutics (Z.Y., E.R., G.A.F.), the Institute for Medicine and Engineering (K.I.-S., P.L.J.), and Department of Pharmacology (Z.Y., E.R., T.M., S.L., W.C.S., R.K.A., G.A.F.), University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Temple University, Philadelphia, PA (G.L., R.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Ricciotti","sequence":"additional","affiliation":[{"name":"From the The Institute for Translational Medicine and Therapeutics (Z.Y., E.R., G.A.F.), the Institute for Medicine and Engineering (K.I.-S., P.L.J.), and Department of Pharmacology (Z.Y., E.R., T.M., S.L., W.C.S., R.K.A., G.A.F.), University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Temple University, Philadelphia, PA (G.L., R.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Miwa","sequence":"additional","affiliation":[{"name":"From the The Institute for Translational Medicine and Therapeutics (Z.Y., E.R., G.A.F.), the Institute for Medicine and Engineering (K.I.-S., P.L.J.), and Department of Pharmacology (Z.Y., E.R., T.M., S.L., W.C.S., R.K.A., G.A.F.), University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Temple University, Philadelphia, PA (G.L., R.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shulin","family":"Liu","sequence":"additional","affiliation":[{"name":"From the The Institute for Translational Medicine and Therapeutics (Z.Y., E.R., G.A.F.), the Institute for Medicine and Engineering (K.I.-S., P.L.J.), and Department of Pharmacology (Z.Y., E.R., T.M., S.L., W.C.S., R.K.A., G.A.F.), University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Temple University, Philadelphia, PA (G.L., R.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Ihida-Stansbury","sequence":"additional","affiliation":[{"name":"From the The Institute for Translational Medicine and Therapeutics (Z.Y., E.R., G.A.F.), the Institute for Medicine and Engineering (K.I.-S., P.L.J.), and Department of Pharmacology (Z.Y., E.R., T.M., S.L., W.C.S., R.K.A., G.A.F.), University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Temple University, Philadelphia, PA (G.L., R.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin","family":"Landesberg","sequence":"additional","affiliation":[{"name":"From the The Institute for Translational Medicine and Therapeutics (Z.Y., E.R., G.A.F.), the Institute for Medicine and Engineering (K.I.-S., P.L.J.), and Department of Pharmacology (Z.Y., E.R., T.M., S.L., W.C.S., R.K.A., G.A.F.), University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Temple University, Philadelphia, PA (G.L., R.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter L.","family":"Jones","sequence":"additional","affiliation":[{"name":"From the The Institute for Translational Medicine and Therapeutics (Z.Y., E.R., G.A.F.), the Institute for Medicine and Engineering (K.I.-S., P.L.J.), and Department of Pharmacology (Z.Y., E.R., T.M., S.L., W.C.S., R.K.A., G.A.F.), University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Temple University, Philadelphia, PA (G.L., R.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosario","family":"Scalia","sequence":"additional","affiliation":[{"name":"From the The Institute for Translational Medicine and Therapeutics (Z.Y., E.R., G.A.F.), the Institute for Medicine and Engineering (K.I.-S., P.L.J.), and Department of Pharmacology (Z.Y., E.R., T.M., S.L., W.C.S., R.K.A., G.A.F.), University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Temple University, Philadelphia, PA (G.L., R.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Chao","family":"Song","sequence":"additional","affiliation":[{"name":"From the The Institute for Translational Medicine and Therapeutics (Z.Y., E.R., G.A.F.), the Institute for Medicine and Engineering (K.I.-S., P.L.J.), and Department of Pharmacology (Z.Y., E.R., T.M., S.L., W.C.S., R.K.A., G.A.F.), University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Temple University, Philadelphia, PA (G.L., R.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard K","family":"Assoian","sequence":"additional","affiliation":[{"name":"From the The Institute for Translational Medicine and Therapeutics (Z.Y., E.R., G.A.F.), the Institute for Medicine and Engineering (K.I.-S., P.L.J.), and Department of Pharmacology (Z.Y., E.R., T.M., S.L., W.C.S., R.K.A., G.A.F.), University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Temple University, Philadelphia, PA (G.L., R.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garret A.","family":"FitzGerald","sequence":"additional","affiliation":[{"name":"From the The Institute for Translational Medicine and Therapeutics (Z.Y., E.R., G.A.F.), the Institute for Medicine and Engineering (K.I.-S., P.L.J.), and Department of Pharmacology (Z.Y., E.R., T.M., S.L., W.C.S., R.K.A., G.A.F.), University of Pennsylvania, Philadelphia, PA; 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