{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:35:19Z","timestamp":1790494519912,"version":"4.1.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Inactivating mutations in matrix Gla protein (MGP) lead to Keutel syndrome, a rare disease hallmarked by ectopic calcification of cartilage and vascular tissues. Although MGP acts as a strong inhibitor of arterial elastic lamina calcification (elastocalcinosis), its mode of action is unknown. Two sets of conserved residues undergoing posttranslational modifications\u20144 glutamic acid residues, which are \u03b3-carboxylated by gamma-glutamyl carboxylase; and 3 serine residues, which are phosphorylated by yet unknown kinase(s)\u2014are thought to be essential for MGP\u2019s function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We pursued a genetic approach to study the roles of MGP\u2019s conserved residues. First, a transgenic line (\n                      <jats:italic>SM22a-GlamutMgp<\/jats:italic>\n                      ) expressing a mutant form of MGP, in which the conserved glutamic acid residues were mutated to alanine, was generated. The transgene was introduced to\n                      <jats:italic>\n                        Mgp\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice to generate a compound mutant, which produced the mutated MGP only in the vascular tissues. We generated a second mouse model (\n                      <jats:italic>\n                        Mgp\n                        <jats:sup>S3mut\/S3mut<\/jats:sup>\n                      <\/jats:italic>\n                      ) to mutate MGP\u2019s conserved serine residues to alanine. The initiation and progression of vascular calcification in these models were analyzed by alizarin red staining, histology, and micro-computed tomography imaging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      On a regular diet, the arterial walls in the\n                      <jats:italic>\n                        Mgp\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      ;\n                      <jats:italic>SM22\u03b1-GlamutMgp<\/jats:italic>\n                      mice were not calcified. However, on a high phosphorus diet, these mice showed wide-spread arterial calcification. In contrast,\n                      <jats:italic>\n                        Mgp\n                        <jats:sup>S3mut\/S3mut<\/jats:sup>\n                      <\/jats:italic>\n                      mice on a regular diet recapitulated arterial calcification traits of\n                      <jats:italic>\n                        Mgp\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice, although with lesser severity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>For the first time, we show here that MGP\u2019s conserved serine residues are indispensable for its antimineralization function in the arterial tissues. Although the conserved glutamic acid residues are not essential for this function on a regular diet, they are needed to prevent phosphate-induced arterial elastocalcinosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.122.317518","type":"journal-article","created":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T05:00:58Z","timestamp":1649912458000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Prevention of Arterial Elastocalcinosis: Differential Roles of the Conserved Glutamic Acid and Serine Residues of Matrix Gla Protein"],"prefix":"10.1161","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2517-2592","authenticated-orcid":true,"given":"Abhinav","family":"Parashar","sequence":"first","affiliation":[{"name":"Faculty of Dental Medicine and Oral Health Sciences (A.P., M.M.), McGill University, Montreal, Qu\u00e9bec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6762-8263","authenticated-orcid":true,"given":"Kyoungmi","family":"Bak","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology (K.B., M.M.), McGill University, Montreal, Qu\u00e9bec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0156-0758","authenticated-orcid":true,"given":"Monzur","family":"Murshed","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine and Oral Health Sciences (A.P., M.M.), McGill University, Montreal, Qu\u00e9bec, Canada."},{"name":"Department of Anatomy and Cell Biology (K.B., M.M.), McGill University, Montreal, Qu\u00e9bec, Canada."},{"name":"Department of Medicine (M.M.), McGill University, Montreal, Qu\u00e9bec, Canada."},{"name":"Shriners Hospital for Children, Montreal, Qu\u00e9bec, Canada (M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2010.115"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000249379.55535.21"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612820666140212205848"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000110786.02097.0c"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.114.002262"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.302523"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.87.11.1055"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.19.8.1852"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/hq1201.100229"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a031229"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10669"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2039"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/386078a0"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01958278"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560030511"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291x(83)91663-7"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.44701"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/s8756-3282(02)00821-9"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.18.9.1400"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2003.00023.x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000173313.46222.43"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02758.x"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200402046"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)95688-7"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja207628k"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2020.107637"},{"key":"e_1_3_3_28_2","first-page":"691","article-title":"Fetal warfarin syndrome.","volume":"27","author":"Hou JW","year":"2004","unstructured":"Hou, JW. 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