Acute Effects of Urolithin A on Mitochondrial Respiration in Vascular Smooth Muscle Cells of ApoE-/- Mice

NutritionChronic disease
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Background: During atherosclerotic plaque development, vascular smooth muscle cells (VSMC) undergo dedifferentiation, resulting in a synthetic, less contractile progenitor state. This transition is marked by changes in mitochondrial respiration and increased reactive oxygen species (ROS) production. These changes in bioenergetics play a critical role in atherogenesis via facilitation of VSMC migration towards the intima. 

Objective: The objective of this study was to evaluate the effect Urolithin A (UA), an antioxidant, has on mitochondrial respiration in VSMCs derived from a murine model of atherosclerosis.

Methods: Tissue samples of the descending aorta were extracted from 1-2-month-old ApoE-/- mice. The exposure group (EXP) received 0.0398 mg of UA per mg of aortic tissue while only the vehicle, Dimethyl Sulfoxide (DMSO), was added to the control group (CON). Complex I of the electron transport chain was then activated in an ADP restricted environment via sequential addition of malate (2 mM), pyruvate (6 mM), and glutamate (10 mM). ATP synthase and Complex II were activated via addition of ADP (5 mM) and succinate (10 mM) respectively. Integrity of the outer mitochondrial membrane was tested by addition of cytochrome C (10 μM).

Results: Addition of UA significantly reduced maximal mitochondrial respiration during parallel electron transport through Complex I and II with a mean decrease of 2.665 pmol/s*mg (p<0.05) compared to the CON group. A trend towards reduced Complex V mediated respiration in the EXP group compared to the CON was also observed with a mean difference of 0.7807 pmol/s*mg (p=0.377), along with a decrease in the acceptor control ratio (ACR) of the EXP group with a mean difference of 0.6663 (p=0.112) compared to the CON group.

Conclusions: Acute exposure of UA in aortic VSMCs significantly reduces complex II respiration however, further research


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