Abstract
Cardiac fibrosis occurs after pathological stimuli to the cardiovascular system. One of the most important factors that contribute to cardiac fibrosis is angiotensin II (AngII). Accumulating studies have suggested that reactive oxygen species (ROS) plays an important role in cardiac fibrosis and sodium tanshinone IIA sulfonate (STS) possesses antioxidant action. We therefore examined whether STS depresses Ang II-induced collagen type I expression in cardiac fibroblasts. In this study, Ang II significantly enhanced collagen type I expression and collagen synthesis. Meanwhile, Ang II depressed matrix metalloproteinase-1 (MMP-1) expression and activity. These responses were attenuated by STS. Furthermore, STS depressed the intracellular generation of ROS, NADPH oxidase activity and subunit p47(phox) expression. In addition, N-acetylcysteine the ROS scavenger, depressed effects of Ang II in a manner similar to STS. In conclusion, the current studies demonstrate that anti-fibrotic effects of STS are mediated by interfering with the modulation of ROS.
Highlights
Cardiac fibrosis is characterized by a disproportionate accumulation of extracellular matrix (ECM) proteins that occurs after myocyte death, inflam mation, hypertrophy, and stimulation by a number of hormones, cytokines, and growth factors (Wood, 2002; Kass et al, 2004; Jaana et al, 2005)
On treatment with Ang angiotensin II (II), there was a marked increase in intracellular production of reactive oxygen species (ROS), which played a key role in cardiac fibrosis
As sodium tanshinone IIA sulfonate (STS) was shown to possess some antioxidant action, we examined the effect of STS (3, 10, 30 μM) on angiotensin II (Ang II)-increased intracellular ROS generation
Summary
Cardiac fibrosis is characterized by a disproportionate accumulation of extracellular matrix (ECM) proteins that occurs after myocyte death, inflam mation, hypertrophy, and stimulation by a number of hormones, cytokines, and growth factors (Wood, 2002; Kass et al, 2004; Jaana et al, 2005). Among the ECM proteins, collagens constitute up to 85% (Brown, 2005). As in the form of thick fiber with a high tensile strength, collagen type I content is considered a major determinant of myocardial stiffness. Cardiac fibroblasts (CFs) are the major source of collagen in the myocardium. Collagen type I accumulation in the heart depends on its production, and on its degradation, which is performed by proteinases, such as matrix metalloproteinase-1 (MMP-1) (Heeneman et al, 2003)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
