Abstract 13292: Transplant of Mitochondria to Vascular Endothelial Cells
Mitochondrial dysfunction has adverse consequences on physiological function of vascular endothelial cells. Moreover, intracellular localization of mitochondria restricts pharmacological modifications of mitochondrial function. Therefore, we hypothesized that mitochondrial dysfunction, as expressed by energy deficit, may be corrected by a non-invasive delivery of exogenous biochemically active mitochondria using liposomal delivery system. Recipient cells were human coronary artery endothelial cells from hypertensive donors (HT) and endothelial cells from normotensive donors (NT) that were depleted of mitochondrial DNA (NT-ρ0). Liposomes were prepared from phosphatidylcholine, and combined with isolated mitochondria at 1:1 ratio to form a mitochondria-liposome complex (Mito-Lipo). Under control conditions, intracellular ATP level (ATPi) measured in NT cells was 14.1 ± 1.4 (n = 59), and was lower in HT cells by 30% (9.8 ± 0.5, n = 81, P < 0.05), and by 80% in NT- ρ0 cells (2.8 ± 0.2 nmol/mg protein, n = 70, P < 0.05 vs. NT). In HT cells, ATPi measured 24 hours after treatment with 1-, 5-, 15-, and 25-µl of Mito-Lipo increased from 6.2 ± 0.4 (n = 133) to 8.7 ± 0.9, 11.7 ± 0.8, 14.37 ± 1.8, and 13.5 ± 2.0 nmol/mg protein (n = 25-35, P< 0.05 vs. control), respectively. In NT-ρ0 cells, 24 hours after Mito-Lipo treatment, ATPi increased from 4.4 ± 0.7 to 9.1 ± 2.6, 12.8 ± 3.0, and 10.8 ± 2.2 nmol/mg protein, respectively (n = 70-100/data point, P < 0.05 vs. control) in cells treated with 5-, 15-, and 25-ul of complex. Treatment of HT or NT-ρ0 cells with Mito-Lipo significantly increased cells' proliferation (n=3, P<0.05) and (n=4, P<0.05), respectively. Thus, we present the evidence that a transplant of organella between cells is possible, and may become of significant value in designing new therapeutic strategies for alleviation of mitochondrial dysfunction and bioenergetic failure (ATP) observed in a variety of cardiovascular diseases.
- © 2011 by American Heart Association, Inc.