Key result
Cyclophilin A deficiency in Apoe-/- mice resulted in significantly less Angiotensin II-induced cardiac hypertrophy compared to Apoe-/- mice with intact Cyclophilin A.
Why the study?
Does Cyclophilin A deficiency prevent Angiotensin II-induced cardiac hypertrophy in ApoE-deficient mice?
Does Cyclophilin A deficiency prevent Angiotensin II-induced cardiac hypertrophy in ApoE-deficient mice?
Cyclophilin A is required for Angiotensin II-mediated cardiac hypertrophy in the setting of high ROS and inflammation, suggesting a potential mechanistic target for preventing adverse cardiac remodeling.
Findings do not support CyPA targeting for hypertrophy; leaves open its cardiac role in other models.
OBJECTIVE: Cyclophilin A (CyPA, encoded by Ppia) is a proinflammatory protein secreted in response to oxidative stress in mice and humans. We recently demonstrated that CyPA increased angiotensin II (Ang II)-induced reactive oxygen species (ROS) production in the aortas of apolipoprotein E (Apoe)-/- mice. In this study, we sought to evaluate the role of CyPA in Ang II-induced cardiac hypertrophy. METHODS AND RESULTS: Cardiac hypertrophy was not significantly different between Ppia+/+ and Ppia-/- mice infused with Ang II (1000 ng/min per kg for 4 weeks). Therefore, we investigated the effect of CyPA under conditions of high ROS and inflammation using the Apoe-/- mice. In contrast to Apoe-/- mice, Apoe-/-Ppia-/- mice exhibited significantly less Ang II-induced cardiac hypertrophy. Bone marrow cell transplantation showed that CyPA in cells intrinsic to the heart plays an important role in the cardiac hypertrophic response. Ang II-induced ROS production, cardiac fibroblast proliferation, and cardiac fibroblast migration were markedly decreased in Apoe-/-Ppia-/- cardiac fibroblasts. Furthermore, CyPA directly induced the hypertrophy of cultured neonatal cardiac myocytes. CONCLUSIONS: CyPA is required for Ang II-mediated cardiac hypertrophy by directly potentiating ROS production, stimulating the proliferation and migration of cardiac fibroblasts, and promoting cardiac myocyte hypertrophy.
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Satoh et al. (2011) studied Cardiac hypertrophy. Cyclophilin A deficiency (Ppia-/-) vs. Apoe-/- mice (intact Cyclophilin A) was evaluated on Angiotensin II-induced cardiac hypertrophy. Cyclophilin A deficiency in Apoe-/- mice resulted in significantly less Angiotensin II-induced cardiac hypertrophy compared to Apoe-/- mice with intact Cyclophilin A.
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