title: LOX-1 deletion alters signals of myocardial remodeling immediately after ischemia-reperfusion.
abstract: OBJECTIVE
  Chronic ischemia is associated with alterations in genes that result in myocardial remodeling. An important biochemical basis of cardiac remodeling is generation of reactive oxygen species (ROS). A few studies have suggested that acute ischemia triggers signals for remodeling. We examined the hypothesis that targeted deletion of lectin-like oxidized-LDL receptor (LOX-1) may inhibit signals related to cardiac remodeling.
  
  
  RESULTS
  We generated LOX-1 knockout (KO) mice on C57BL/6 (wild-type mice) background, and subjected wild-type and KO mice to ischemia-reperfusion (I-R). The wild-type mice developed a marked reduction in left ventricular systolic pressure and +/-dp/dt(max) and an increase in left ventricular end-diastolic pressure following I-R, and this change was much less in the LOX-1 KO mice, indicating preservation of left ventricular function with LOX-1 deletion. There was evidence for marked oxidative stress (NADPH oxidase expression, malondialdehyde and 8-isoprostane) following I-R in the wild-type mice, much less so in the LOX-1 KO mice (P<0.01). In concert, collagen deposition (Masson's trichrome and Picro-sirius red staining) increased dramatically in the wild-type mice, but only half as much in the LOX-1 KO mice (P<0.01). Collagen staining data was corroborated with procollagen-I expression. Further, fibronectin and osteopontin expression increased in the wild-type mice, but to a much smaller extent in the LOX-1 KO mice (P<0.01).
  
  
  CONCLUSIONS
  These findings provide compelling evidence that LOX-1 is a key modulator of cardiac remodeling which starts immediately following I-R.
authors: Department of Internal Medicine, University of Arkansas for Medical Sciences, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205-7199, USA.
authors: Changping
authors: C
authors: Hu
authors: Abhijit
authors: A
authors: Dandapat
authors: Jiawei
authors: J
authors: Chen
authors: Yoshiko
authors: Y
authors: Fujita
authors: Nobutaka
authors: N
authors: Inoue
authors: Yosuke
authors: Y
authors: Kawase
authors: Kou-ichi
authors: K
authors: Jishage
authors: Hiroshi
authors: H
authors: Suzuki
authors: Tatsuya
authors: T
authors: Sawamura
authors: Jawahar L
authors: JL
authors: Mehta
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics; D045726:Metalloproteases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000209:etiology*; D053495:Osteopontin / Q000235:genetics; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000032:analysis; D051127:Scavenger Receptors, Class E / Q000502:physiology*; D015398:Signal Transduction; D020257:Ventricular Remodeling
chemical_list: D024042:Collagen Type I; D005353:Fibronectins; C495138:Olr1 protein, mouse; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E; D053495:Osteopontin; D045726:Metalloproteases