{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:36:00Z","timestamp":1791329760770,"version":"4.3.1"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2009,4,21]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    The volume overload of isolated mitral regurgitation (MR) in the dog results in left ventricular (LV) dilatation and interstitial collagen loss. To better understand the mechanism of collagen loss, we performed a gene array and overlaid regulated genes into ingenuity pathway analysis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods and Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Gene arrays from LV tissue were compared in 4 dogs before and 4 months after MR. Cine-magnetic resonance\u2013derived LV end-diastolic volume increased 2-fold (\n                    <jats:italic>P<\/jats:italic>\n                    =0.005), and LV ejection fraction increased from 41% to 53% (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.007). LV interstitial collagen decreased 40% (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05) compared with controls, and replacement collagen was in short strands and in disarray. Ingenuity pathway analysis identified Marfan syndrome, aneurysm formation, LV dilatation, and myocardial infarction, all of which have extracellular matrix protein defects and\/or degradation. Matrix metalloproteinase-1 and -9 mRNA increased 5- (\n                    <jats:italic>P<\/jats:italic>\n                    =0.01) and 10-fold (\n                    <jats:italic>P<\/jats:italic>\n                    =0.003), whereas collagen I did not change and collagen III mRNA increased 1.5-fold (\n                    <jats:italic>P<\/jats:italic>\n                    =0.02). However, noncollagen genes important in extracellular matrix structure were significantly downregulated, including decorin, fibulin 1, and fibrillin 1. In addition, connective tissue growth factor and plasminogen activator inhibitor were downregulated, along with multiple genes in the transforming growth factor-\u03b2 signaling pathway, resulting in decreased LV transforming growth factor-\u03b21 activity (\n                    <jats:italic>P<\/jats:italic>\n                    =0.03).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusions\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    LV collagen loss in isolated, compensated MR is chiefly due to posttranslational processing and degradation. The downregulation of multiple noncollagen genes important in global extracellular matrix structure, coupled with decreased expression of multiple profibrotic factors, explains the failure to replace interstitial collagen in the MR heart.\n                  <\/jats:p>","DOI":"10.1161\/circulationaha.108.826230","type":"journal-article","created":{"date-parts":[[2009,4,6]],"date-time":"2009-04-06T21:36:09Z","timestamp":1239053769000},"page":"2086-2095","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":90,"title":["Microarray Identifies Extensive Downregulation of Noncollagen Extracellular Matrix and Profibrotic Growth Factor Genes in Chronic Isolated Mitral Regurgitation in the Dog"],"prefix":"10.1161","volume":"119","author":[{"given":"Junying","family":"Zheng","sequence":"first","affiliation":[{"name":"From the Center for Heart Failure Research, Departments of Medicine (J.Z., Y.C., B.P., L.A.D., P.C.P., K.S., N.S., A.H., L.J.D.) and Physiology and Biophysics (A.H.), University of Alabama at Birmingham; Birmingham Department of Veteran Affairs, Birmingham, Ala (L.J.D.); and Auburn University College of Veterinary Medicine (M.T., A.R.D.) and School of Engineering (T.D.), Auburn, Ala."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanwen","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Departments of Medicine (J.Z., Y.C., B.P., L.A.D., P.C.P., K.S., N.S., A.H., L.J.D.) and Physiology and Biophysics (A.H.), University of Alabama at Birmingham; Birmingham Department of Veteran Affairs, Birmingham, Ala (L.J.D.); and Auburn University College of Veterinary Medicine (M.T., A.R.D.) and School of Engineering (T.D.), Auburn, Ala."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty","family":"Pat","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Departments of Medicine (J.Z., Y.C., B.P., L.A.D., P.C.P., K.S., N.S., A.H., L.J.D.) and Physiology and Biophysics (A.H.), University of Alabama at Birmingham; Birmingham Department of Veteran Affairs, Birmingham, Ala (L.J.D.); and Auburn University College of Veterinary Medicine (M.T., A.R.D.) and School of Engineering (T.D.), Auburn, Ala."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis A.","family":"Dell'Italia","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Departments of Medicine (J.Z., Y.C., B.P., L.A.D., P.C.P., K.S., N.S., A.H., L.J.D.) and Physiology and Biophysics (A.H.), University of Alabama at Birmingham; Birmingham Department of Veteran Affairs, Birmingham, Ala (L.J.D.); and Auburn University College of Veterinary Medicine (M.T., A.R.D.) and School of Engineering (T.D.), Auburn, Ala."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Tillson","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Departments of Medicine (J.Z., Y.C., B.P., L.A.D., P.C.P., K.S., N.S., A.H., L.J.D.) and Physiology and Biophysics (A.H.), University of Alabama at Birmingham; Birmingham Department of Veteran Affairs, Birmingham, Ala (L.J.D.); and Auburn University College of Veterinary Medicine (M.T., A.R.D.) and School of Engineering (T.D.), Auburn, Ala."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Ray","family":"Dillon","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Departments of Medicine (J.Z., Y.C., B.P., L.A.D., P.C.P., K.S., N.S., A.H., L.J.D.) and Physiology and Biophysics (A.H.), University of Alabama at Birmingham; Birmingham Department of Veteran Affairs, Birmingham, Ala (L.J.D.); and Auburn University College of Veterinary Medicine (M.T., A.R.D.) and School of Engineering (T.D.), Auburn, Ala."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela C.","family":"Powell","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Departments of Medicine (J.Z., Y.C., B.P., L.A.D., P.C.P., K.S., N.S., A.H., L.J.D.) and Physiology and Biophysics (A.H.), University of Alabama at Birmingham; Birmingham Department of Veteran Affairs, Birmingham, Ala (L.J.D.); and Auburn University College of Veterinary Medicine (M.T., A.R.D.) and School of Engineering (T.D.), Auburn, Ala."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Shi","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Departments of Medicine (J.Z., Y.C., B.P., L.A.D., P.C.P., K.S., N.S., A.H., L.J.D.) and Physiology and Biophysics (A.H.), University of Alabama at Birmingham; Birmingham Department of Veteran Affairs, Birmingham, Ala (L.J.D.); and Auburn University College of Veterinary Medicine (M.T., A.R.D.) and School of Engineering (T.D.), Auburn, Ala."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Shah","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Departments of Medicine (J.Z., Y.C., B.P., L.A.D., P.C.P., K.S., N.S., A.H., L.J.D.) and Physiology and Biophysics (A.H.), University of Alabama at Birmingham; Birmingham Department of Veteran Affairs, Birmingham, Ala (L.J.D.); and Auburn University College of Veterinary Medicine (M.T., A.R.D.) and School of Engineering (T.D.), Auburn, Ala."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Denney","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Departments of Medicine (J.Z., Y.C., B.P., L.A.D., P.C.P., K.S., N.S., A.H., L.J.D.) and Physiology and Biophysics (A.H.), University of Alabama at Birmingham; Birmingham Department of Veteran Affairs, Birmingham, Ala (L.J.D.); and Auburn University College of Veterinary Medicine (M.T., A.R.D.) and School of Engineering (T.D.), Auburn, Ala."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahsan","family":"Husain","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Departments of Medicine (J.Z., Y.C., B.P., L.A.D., P.C.P., K.S., N.S., A.H., L.J.D.) and Physiology and Biophysics (A.H.), University of Alabama at Birmingham; Birmingham Department of Veteran Affairs, Birmingham, Ala (L.J.D.); and Auburn University College of Veterinary Medicine (M.T., A.R.D.) and School of Engineering (T.D.), Auburn, Ala."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis J.","family":"Dell'Italia","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Departments of Medicine (J.Z., Y.C., B.P., L.A.D., P.C.P., K.S., N.S., A.H., L.J.D.) and Physiology and Biophysics (A.H.), University of Alabama at Birmingham; Birmingham Department of Veteran Affairs, Birmingham, Ala (L.J.D.); and Auburn University College of Veterinary Medicine (M.T., A.R.D.) and School of Engineering (T.D.), Auburn, Ala."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1995.269.2.H571"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.38.3.172"},{"key":"e_1_3_2_3_2","first-page":"H2065","volume":"269","year":"1995","unstructured":"Dell'Italia LJ, Meng QC, Balcells E, Straeter-Knowlen IM, Hankes GH, Dillon R, Cartee RE, Orr R, Bishop SP, Oparil S, et al. 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