{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:05:37Z","timestamp":1791313537496,"version":"4.3.1"},"reference-count":84,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:p>\n                    In hypertension, an increase in arterial wall thickness and loss of elasticity over time result in an increase in pulse wave velocity, a direct measure of arterial stiffness. This change is reflected in gradual fragmentation and loss of elastin fibers and accumulation of stiffer collagen fibers in the media that occurs independently of atherosclerosis. Similar results are seen with an elevated level of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), which increases vascular thickness, elastin fragmentation, and arterial blood pressure. Studies from our laboratory have demonstrated a decrease in elasticity and an increase in pulse wave velocity in HHcy cystathionine\n                    <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                    synthase heterozygote knockout (CBS\n                    <jats:sup>\u2212\/+<\/jats:sup>\n                    ) mice. Nitric oxide (NO) is a potential regulator of matrix metalloproteinase (MMP) activity in MMP-NO-TIMP (tissue inhibitor of metalloproteinase) inhibitory tertiary complex. We have demonstrated the contribustion of the NO synthase (NOS) isoforms, endothelial NOS and inducible NOS, in the activation of latent MMP. The differential production of NO contributes to oxidative stress and increased oxidative\/nitrative activation of MMP resulting in vascular remodeling in response to HHcy. The contribution of the NOS isoforms, endothelial and inducible in the collagen\/elastin switch, has been demonstrated. We have showed that an increase in inducible NOS activity is a key contributor to HHcy-mediated collagen\/elastin switch and resulting decline in aortic compliance. In addition, increased levels of Hcy compete and suppress the\n                    <jats:italic toggle=\"yes\">\u03b3<\/jats:italic>\n                    -amino butyric acid-receptor,\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    -methyl-\n                    <jats:sc>d<\/jats:sc>\n                    -aspartate-receptor, and peroxisome proliferator-activated receptor. The HHcy causes oxidative stress by generating nitrotyrosine, activating the latent MMPs and decreasing the endothelial NO concentration. The HHcy causes elastinolysis and decrease elastic complicance of the vessel wall. The treatment with\n                    <jats:italic toggle=\"yes\">\u03b3<\/jats:italic>\n                    -amino butyric acid-receptor agonist (muscimol),\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    -methyl-\n                    <jats:sc>d<\/jats:sc>\n                    -aspartate-receptor antagonist (MK-801), and peroxisome proliferator-activated receptor agonists (ciprofibrate and ciglitazone) mitigates the cardiovascular dysfunction in HHcy.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    15, 1927\u20131943.\n                  <\/jats:p>","DOI":"10.1089\/ars.2010.3721","type":"journal-article","created":{"date-parts":[[2010,12,2]],"date-time":"2010-12-02T23:38:52Z","timestamp":1291333132000},"page":"1927-1943","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":153,"title":["Mechanisms of Cardiovascular Remodeling in Hyperhomocysteinemia"],"prefix":"10.1177","volume":"15","author":[{"given":"Mesia M.","family":"Steed","sequence":"first","affiliation":[{"name":"University of Louisville School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh C.","family":"Tyagi","sequence":"additional","affiliation":[{"name":"University of Louisville School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2011,10,1]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2003.10.042"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199704173361601"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.4.5.2407589"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx9501445"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/41.6.948"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)76074-2"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3109\/00365519709084603"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.37.195.505"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM193311232092110"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2005.02.021"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2000-8469"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)75871-7"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-131-5-199909070-00008"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205256200"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000063607.56590.7F"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0955-2863(90)90070-2"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/PL00014300"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V12102181"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2001.115"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(62)90114-6"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199405193302008"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.2.1.3335280"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1983.tb07850.x"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.359"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.2005.044610"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-1-3"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2891-3-4"},{"key":"e_1_3_2_29_2","first-page":"433","volume-title":"Oxy-radicals in Molecular Biology and Pathology","author":"Heinecke JS","year":"1988","unstructured":"Heinecke JS. 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