Key result
Angiotensin II significantly increased cardiac fibroblast proliferation, migration, and collagen production, which were effectively inhibited by the AT1 receptor blocker telmisartan and CD44 gene silencing.
Why the study?
The cellular and molecular mechanisms underlying Angiotensin II-induced cardiac fibrosis were not well understood.
AT1 receptor antagonism and CD44 silencing inhibit Ang II-induced cardiac fibroblast activation and collagen production, highlighting potential therapeutic targets for cardiac fibrosis.
Angiotensin II (Ang II) is known to elicit cardiac fibrosis by activating the AT1 receptor and CD44 expression in the in vivo model. However, the cellular/molecular mechanisms underlying cardiac fibrosis are still not well understood. This study examines the roles of the AT1 receptor and CD44 gene expression in collagen synthesis through Ang II stimulated cardiac fibroblasts. Fibroblasts were isolated from the neonatal rat hearts; the activation of fibroblasts was evaluated using the assays of cell viability and migration, and silencing of CD44 gene expression was conducted with small interfering RNA (siRNA). Results showed that Ang II significantly increases the cell proliferation and migration in a dose-dependent manner. Upon activation, the protein levels of TGF-β1, Smad2, Smad4 and collagen I were significantly increased (all p by the AT1 receptor blocker, telmisartan (all p β1 as demonstrated by Pearson correlation analysis (r = 0.955, p < 0.01). Gene transfection of fibroblasts with Ad-CD44 siRNA, as evidenced by low levels of CD44 mRNA and protein, significantly reduced the production of collagen I. In summary, these results indicate that the proliferation, migration and collagen production from Ang II activated cardiac fibroblasts are potentially mediated by the AT1 receptor and CD44. Such a signaling mechanism could be crucial for the production of collagen and the development of tissue fibrosis in the heart.
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Bai et al. (2020) studied Cardiac fibrosis (in vitro model). Angiotensin II, Telmisartan, and CD44 siRNA vs. Unstimulated cells was evaluated on Protein levels of TGF-β1, Smad2, Smad4 and collagen I (p=<0.05). Angiotensin II significantly increased cardiac fibroblast proliferation, migration, and collagen production, which were effectively inhibited by the AT1 receptor blocker telmisartan and CD44 gene silencing.
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