{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:58:26Z","timestamp":1790618306680,"version":"4.1.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"25","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2000,12,19]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>\u2014Prostacyclin has proved to be a beneficial treatment for patients with severe pulmonary hypertension. We postulated that the response may reflect, at least in part, inhibition of pulmonary artery smooth muscle cell (PASMC) growth.<\/jats:p><jats:p><jats:italic>Methods and Results<\/jats:italic>\u2014Human PASMCs were derived from distal (&lt;1-mm external diameter, n=8) and proximal (&gt;8-mm external diameter, n=12) pulmonary arteries obtained at transplant surgery and pneumonectomy. The effects of the stable prostacyclin analogues on [<jats:italic>methyl<\/jats:italic>-<jats:sup>3<\/jats:sup>H]thymidine incorporation and cell proliferation were investigated by using immunohistochemically characterized cells. Distal cells proliferated faster than did proximal PASMCs and displayed a distinct sensitivity to cicaprost and iloprost. Both analogues inhibited thymidine uptake over 24 hours (20% to 60%,<jats:italic>P<\/jats:italic>&lt;0.001; n=8) and abolished stimulation of DNA synthesis by platelet-derived growth factor-BB (10 ng\/mL) in distal but not proximal cells. The inhibitory effect of cicaprost was mimicked by isoproterenol (10<jats:sup>\u22125<\/jats:sup>mol\/L), forskolin (10<jats:sup>\u22125<\/jats:sup>mol\/L), and dibutyryl cAMP (5\u00d710<jats:sup>\u22124<\/jats:sup>mol\/L) and was potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (5\u00d710<jats:sup>\u22125<\/jats:sup>mol\/L). Cicaprost (10<jats:sup>\u221210<\/jats:sup>to 10<jats:sup>\u22126<\/jats:sup>mol\/L) inhibited the proliferation of PASMCs, which had been stimulated with either platelet-derived growth factor-BB or serum, and increased cAMP production. These effects were potentiated by 3-isobutyl-1-methylxanthine and attenuated by the adenylyl cyclase inhibitor 2\u2032,5\u2032-dideoxyadenosine (10<jats:sup>\u22125<\/jats:sup>to 10<jats:sup>\u22124<\/jats:sup>mol\/L).<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>\u2014Cicaprost and iloprost inhibit DNA synthesis and proliferation to a greater extent in distal compared with proximal human PASMCs, acting at least in part via a cAMP-dependent mechanism. The results are consistent with the hypothesis that prostacyclin analogues inhibit vascular remodeling in pulmonary hypertension and demonstrate heterogeneity among human PASMCs.<\/jats:p>","DOI":"10.1161\/01.cir.102.25.3130","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"3130-3136","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":119,"title":["Prostacyclin Analogues Differentially Inhibit Growth of Distal and Proximal Human Pulmonary Artery Smooth Muscle Cells"],"prefix":"10.1161","volume":"102","author":[{"given":"John","family":"Wharton","sequence":"first","affiliation":[{"name":"From the Department of Histochemistry (J.W., N.D., J.M.P.), the Section on Clinical Pharmacology (P.D.U., N.W.M.), and the Department of Cardiothoracic Surgery (M.H.Y.), Imperial College School of Medicine, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Davie","sequence":"additional","affiliation":[{"name":"From the Department of Histochemistry (J.W., N.D., J.M.P.), the Section on Clinical Pharmacology (P.D.U., N.W.M.), and the Department of Cardiothoracic Surgery (M.H.Y.), Imperial College School of Medicine, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Upton","sequence":"additional","affiliation":[{"name":"From the Department of Histochemistry (J.W., N.D., J.M.P.), the Section on Clinical Pharmacology (P.D.U., N.W.M.), and the Department of Cardiothoracic Surgery (M.H.Y.), Imperial College School of Medicine, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdi H.","family":"Yacoub","sequence":"additional","affiliation":[{"name":"From the Department of Histochemistry (J.W., N.D., J.M.P.), the Section on Clinical Pharmacology (P.D.U., N.W.M.), and the Department of Cardiothoracic Surgery (M.H.Y.), Imperial College School of Medicine, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia M.","family":"Polak","sequence":"additional","affiliation":[{"name":"From the Department of Histochemistry (J.W., N.D., J.M.P.), the Section on Clinical Pharmacology (P.D.U., N.W.M.), and the Department of Cardiothoracic Surgery (M.H.Y.), Imperial College School of Medicine, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas W.","family":"Morrell","sequence":"additional","affiliation":[{"name":"From the Department of Histochemistry (J.W., N.D., J.M.P.), the Section on Clinical Pharmacology (P.D.U., N.W.M.), and the Department of Cardiothoracic Surgery (M.H.Y.), Imperial College School of Medicine, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115324"},{"key":"e_1_3_2_2_2","first-page":"293","volume":"30","year":"1979","unstructured":"Moncada S, Vane JR. 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