Angiotensin II has multiple profibrotic effects in human cardiac fibroblasts

Area of Science:

• Cardiovascular Biology
• Cellular and Molecular Medicine
• Fibrosis Research

Background:

• Angiotensin II (Ang II) is linked to cardiac remodeling and has profibrotic effects.
• Understanding Ang II's direct impact on human cardiac fibroblasts is crucial for cardiac fibrosis research.

Purpose of the Study:

• To investigate the direct cellular effects of Ang II on human cardiac fibroblasts.
• To determine Ang II's role in fibroblast growth, extracellular matrix accumulation, and adhesion.
• To identify the specific Ang II receptor mediating these effects.

Main Methods:

• Human cardiac fibroblasts were isolated from explanted hearts.
• Cells were treated with Ang II and specific receptor antagonists (irbesartan, PD 123319, divalinil).
• Assays included measurement of mitogen-activated protein kinase activity, DNA synthesis, mRNA levels (TGF-β1, laminin, fibronectin, PAI-1), and fibroblast attachment to collagen.

Main Results:

• Ang II significantly increased fibroblast DNA synthesis, TGF-β1, laminin, and fibronectin mRNA levels.
• Ang II enhanced plasminogen activator inhibitor-1 expression and cardiac fibroblast attachment to collagen.
• These effects were mediated exclusively through the AT(1) receptor, as they were blocked by irbesartan.

Conclusions:

• Activation of the AT(1) receptor by Ang II in human cardiac cells promotes cardiac fibrosis.
• Ang II plays a novel role in stimulating plasminogen activator inhibitor-1 expression.
• Ang II enhances cardiac fibroblast adhesion to collagen, contributing to fibrotic processes.