Abstract 10940: Human Cardiac Biopsy-derived Cells Reduce Angiotensin II-induced Cardiac Remodeling
Purpose: Angiotensin (Ang) II is an important mediator of cardiac remodelling. We identified novel cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs), which share properties with mesenchymal stromal cells. The aim of our study was to evaluate whether CAPs improve Ang II-induced cardiac remodelling.
Methods: CAPs were isolated from human cardiac biopsies. Ang II (1.8 mg/kg body weight/day) or saline were subcutaneously delivered in C57BL/6 mice by an osmotic pump. One week after the Ang II infusion onset, 2 × 10e5 CAPs or PBS were i.m. injected. Two weeks after CAPs/PBS application, left ventricle (LV) function was determined with a conductance catheter and mice were sacrificed. Human Alu presence was quantified via real-time PCR. LV collagen I, III, and α-smooth muscle actin (SMA) expression and (phosphorylated)/total cardiac myosin, Akt, and ERK1 were analyzed by immunohistology and Western Blot, respectively. Direct anti-fibrotic effects of CAPs were evaluated in vitro. In addition, mononuclear cells (MNCs) from all experimental groups were co-cultured with fibroblasts and their effect on collagen production determined.
Results: Cardiac presence of CAPs was confirmed by human Alu detection. CAPs improved LV function in Ang II mice. In parallel, they decreased the LV to body weight ratio and cardiac myosin expression (heavy chain) by 1.2-fold (p<0.05) and 4.7-fold (p<0.001), respectively. Concomitantly, CAPs reduced the phosphorylation of Akt and ERK1 by 1.9-fold and 1.4-fold, respectively (p<0.05 vs Ang II). Furthermore, CAPs decreased LV collagen I and III by 1.5-fold and 2.4-fold in Ang II mice (p<0.01 vs Ang II), respectively, whereas they tendentiously decreased α-SMA expression. In vitro, CAPs supplementation to cardiac fibroblasts decreased the Ang II-induced ROS production, α-SMA expression, fibroblast proliferation, and collagen production by 3.2-fold, 2.1-fold, 1.8-fold, and 1.4-fold, respectively (p<0.05). All anti-fibrotic features of CAPs were mediated in an NO- and IL-10-dependent manner. MNCs from Ang II+CAPs mice induced 2.1-fold (p<0.05) less collagen production in fibroblasts compared to MNCs from Ang II mice.
Conclusion: CAPs improve cardiac remodelling via paracrine actions.
- © 2012 by American Heart Association, Inc.