Back to Search
Start Over
LOX-1 deletion alters signals of myocardial remodeling immediately after ischemia–reperfusion
- Source :
- Cardiovascular Research; Nov2007, Vol. 76 Issue 2, p292-302, 11p
- Publication Year :
- 2007
-
Abstract
- 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. Methods and 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<subscript>max</subscript> 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. [Copyright &y& Elsevier]
- Subjects :
- ISCHEMIA
BLOOD circulation disorders
CONNECTIVE tissues
MUSCULOSKELETAL system
Subjects
Details
- Language :
- English
- ISSN :
- 00086363
- Volume :
- 76
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Cardiovascular Research
- Publication Type :
- Academic Journal
- Accession number :
- 27051658
- Full Text :
- https://doi.org/10.1016/j.cardiores.2007.07.003