Apolipoprotein A1 Enhances Endothelial Cell Survival in anIn VitroModel of ALS

Abstract

AbstractAltered lipoprotein metabolism is considered a pathogenic component of amyotrophic lateral sclerosis (ALS). Apolipoprotein A1 (ApoA1), a major high-density lipoprotein (HDL) protein, is associated with prevention of vascular damage. However, ApoA1’s effects on damaged endothelium in ALS are unknown. This study aimed to determine therapeutic potential of ApoA1 for endothelial cell (EC) repair under a pathologic condition reminiscent of ALS. We performedin vitrostudies using mouse brain ECs (mBECs) exposed to plasma from symptomatic G93A SOD1 mice. Dosage effects of ApoA1, including inhibition of the phosphoinoside 3-kinase (PI3K)/Akt signaling pathway and integration of ApoA1 into mBECs were examined. Also, human bone marrow-derived endothelial progenitor cells (hBM-EPCs) and mBECs were co-cultured without cell contact to establish therapeutic mechanism of hBM-EPC transplantation. Results showed that ApoA1 significantly reduced mBEC death via the PI3K/Akt downstream signaling pathway. Also, ApoA1 was incorporated into mBECs as confirmed by blocked ApoA1 cellular integration. Co-culture system provided evidence that ApoA1 was secreted by hBM-EPCs and incorporated into injured mBECs. Thus, our study findings provide important evidence for ApoA1 as a potential novel therapeutic for endothelium protection in ALS. Thisin vitrostudy lays the groundwork for furtherin vivoresearch to fully determine therapeutic effects of ApoA1 in ALS.