{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T18:10:37Z","timestamp":1767982237137,"version":"3.49.0"},"reference-count":49,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:p>We have reported previously that Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) reduces fibrosis and inflammation (in macrophages and mast cells). However, it is not known whether Ac-SDKP decreases collagen cross-linking and lymphocyte infiltration; lymphocytes modulate both collagen cross-linking and ECM (extracellular matrix) formation in hypertension. Thus we hypothesized that (i) in AngII (angiotensin II)-induced hypertension, Ac-SDKP prevents increases in cross-linked and total collagen by down-regulating LOX (lysyl oxidase), the enzyme responsible for cross-linking, and (ii) these effects are associated with decreased pro-fibrotic cytokine TGF\u03b2 (transforming growth factor \u03b2) and the pro-inflammatory transcription factor NF-\u03baB (nuclear factor \u03baB) and CD4+\/CD8+ lymphocyte infiltration. We induced hypertension in rats by infusing AngII either alone or combined with Ac-SDKP for 3\u00a0weeks. Whereas Ac-SDKP failed to lower BP (blood pressure) or LV (left ventricular) hypertrophy, it did prevent AngII-induced increases in (i) cross-linked and total collagen, (ii) LOX mRNA expression and LOXL1 (LOX-like 1) protein, (iii) TGF\u03b2 expression, (iv) nuclear translocation of NF-\u03baB, (v) CD4+\/CD8+ lymphocyte infiltration, and (vi) CD68+ macrophages infiltration. In addition, we found a positive correlation between CD4+ infiltration and LOXL1 expression. In conclusion, the effect of Ac-SDKP on collagen cross-linking and total collagen may be due to reduced TGF\u03b21, LOXL1, and lymphocyte and macrophage infiltration, and its effect on inflammation could be due to lower NF-\u03baB.<\/jats:p>","DOI":"10.1042\/cs20120619","type":"journal-article","created":{"date-parts":[[2013,7,23]],"date-time":"2013-07-23T18:19:38Z","timestamp":1374603578000},"page":"85-94","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["<i>N<\/i>-acetyl-seryl-aspartyl-lysyl-proline reduces cardiac collagen cross-linking and inflammation in angiotensin II-induced hypertensive rats"],"prefix":"10.1042","volume":"126","author":[{"given":"Germ\u00e1n\u00a0E.","family":"Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, U.S.A."},{"name":"Cardiovascular Pathophysiology Institute, University of Buenos Aires, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nour-Eddine","family":"Rhaleb","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, U.S.A."},{"name":"Department of Physiology, Wayne State University, Detroit, MI 48201, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tang-Dong","family":"Liao","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunhe","family":"Liu","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Leung","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangguo","family":"Dai","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Ping","family":"Yang","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar\u00a0A.","family":"Carretero","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2013,9,9]]},"reference":[{"key":"2021113010312059800_B1","doi-asserted-by":"crossref","first-page":"H1253","DOI":"10.1152\/ajpheart.00481.2008","article-title":"Prevention of aortic fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in angiotensin II-induced hypertension","volume":"295","author":"Lin","year":"2008","journal-title":"Am. 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