{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:43:05Z","timestamp":1777873385857,"version":"3.51.4"},"reference-count":63,"publisher":"Frontiers Media SA","issue":"7","license":[{"start":{"date-parts":[[2009,7,1]],"date-time":"2009-07-01T00:00:00Z","timestamp":1246406400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:p>In hypertension, elevated levels of oxidative\/inflammatory mediators including nuclear factor kappaB (NF-\u03baB), activating protein (AP-1), c-Jun-NH2-terminal kinase (JNK), and cell-regulatory proteins such as transforming growth factor beta (TGF-\u03b2), trigger the mobilization of extracellular matrix (ECM) leading to fibrosis, hypertrophy and impairment of cardiac function. Although the heme oxygenase (HO) system is cytoprotective, its effects on cardiac fibrosis and hypertrophy in deoxycorticosterone acetate (DOCA-salt) hypertension are not completely elucidated. Here, we report cardioprotection by the HO inducer, heme arginate against histopathological lesions in DOCA-hypertension. Treatment with heme arginate restored physiological blood pressure, and abated cardiac hypertrophy (3.75 \u00b1 0.12 vs. 3.19 \u00b1 0.09 g\/kg body wt; n =16, P &lt; 0.01), left-to-right ventricular ratio (6.67 \u00b1 0.62 vs. 4.39 \u00b1 0.63; n = 16, P &lt; 0.01), left ventricular mass (2.48 \u00b1 0.14 vs. 2.01 \u00b1 0.09 g\/kg body wt; n = 16, P &lt; 0.01) and left-ventricular wall thickness (2.82 \u00b1 0.16 vs. 1.98 \u00b1 0.14 mm; n = 16, P &lt; 0.01), whereas the HO inhibitor, chromium mesoporphyrin, exacerbated hypertrophy and cardiac lesions. The suppression of cardiac hypertrophy was accompanied by a robust increase in HO-1, HO activity, cyclic guanosine monophosphate (cGMP), ferritin and the total antioxidant capacity, whereas 8-isoprostane, NF-\u03baB, JNK, AP-1, TGF-\u03b2, fibronectin and collagen-I were significantly abated. Correspondingly, histopathological parameters that depict progressive cardiac damage, including fibrosis, interstitial\/perivascular collagen deposition, scarring, muscle-fiber thickness, muscular hypertrophy and coronary-arteriolar thickening were abated. Our study suggests that upregulating the HO system lowers blood pressure, potentiates the antioxidant status in tissues, suppresses oxidative stress\/mediators such as NF-\u03baB, AP-1 and cJNK, and suppresses the mobilization of ECM proteins like TGF-\u03b2, collagen and fibronectin, with corresponding reduction of cardiac histopathological lesion and hypertrophy.<\/jats:p>","DOI":"10.3181\/0810-rm-302","type":"journal-article","created":{"date-parts":[[2009,5,8]],"date-time":"2009-05-08T22:00:08Z","timestamp":1241820008000},"page":"764-778","source":"Crossref","is-referenced-by-count":25,"title":["Heme Arginate Suppresses Cardiac Lesions and Hypertrophy in Deoxycorticosterone Acetate-Salt Hypertension"],"prefix":"10.3389","volume":"234","author":[{"given":"Ashok","family":"Jadhav","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Saskatchewan College of Medicine, Saskatoon, Saskatchewan, Canada S7N 5E5"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph Fomusi","family":"Ndisang","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Saskatchewan College of Medicine, Saskatoon, Saskatchewan, Canada S7N 5E5"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2009,7,1]]},"reference":[{"key":"bibr-R1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.64.6.1041"},{"key":"bibr-R2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00708.2006"},{"key":"bibr-R3","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.4.C873"},{"key":"bibr-R4","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.2.319"},{"key":"bibr-R6","doi-asserted-by":"publisher","DOI":"10.1161\/hc3001.091458"},{"key":"bibr-R7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01096.2001"},{"key":"bibr-R8","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2006.07.011"},{"key":"bibr-R9","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1994.1098"},{"key":"bibr-R10","doi-asserted-by":"crossref","unstructured":"Lee SW, Han SI, Kim HH, Lee ZH. 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