‘Good Cholesterol’ Protein Improved Blood Vessel Cell Health

ApoA1 can prevent death of endothelial cells, ALS lab study shows

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A scientist conducts tests in a lab using petri dishes and vials of blood.

A cholesterol-related protein, called apolipoprotein A1 (ApoA1), can prevent the death of endothelial cells — those lining blood vessel walls — in a cell model of amyotrophic lateral sclerosis (ALS), a recent lab study shows.

According to researchers, these results “show promise for ApoA1 as a therapeutic agent to restore the damaged endothelium in ALS.”

The study, “Apolipoprotein A1 Enhances Endothelial Cell Survival in an In Vitro Model of ALS,” was published in the journal eNeuro.

ApoA1 is a component of high-density lipoprotein (HDL), which is commonly referred to as “good cholesterol.” Studies have suggested that higher HDL levels are associated with a decreased risk of ALS.

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A trio of scientists at USF Health Morsani College of Medicine in Tampa, Florida conducted a series of experiments in cell models to examine how ApoA1 affects endothelial cells in ALS. These cells are important for protecting cells in the nervous system from toxins, and they commonly show signs of damage in ALS.

“With a functional barrier, the hope is that the environment in the central nervous system will become less toxic and disease progression can be slowed,” Svitlana Garbuzova-Davis, PhD, said in a press release. Garbuzova-Davis is a professor at the department of Neurosurgery and Brain Repair at the University of South Florida and the study’s lead author.

For the experiments, researchers used mouse brain epithelial cells, called mBECs, that were grown in lab dishes. To simulate ALS-like conditions, mBECs were treated with serum (the non-cellular parts of blood) taken from a mouse model of ALS.

Results showed the rates of cell death were significantly higher in mBECs exposed to the animals’ serum (49.46%) than in those grown in normal culture media (6.28%).

Adding ApoA1 to culture media reduced this cell death effect in a dose-dependent manner; at a dosage of 10 micrograms per milliliter (mcg/mL), cell death rate was reduced to 31.12%, and at a concentration of 100 mcg/mL it dropped to 13.51%.

Co-treatment with a chemical that inhibits the PI3K/Akt signaling pathway led to an increase in cell death (39.82%) in mBECs treated with ApoA1. This suggests that ApoA1 exerts its effects at least in part by activating the PI3K/Akt pathway.

“Together, these results showed that ApoA1 mediated [endothelial cell] survival under pathologic [disease-like] conditions and the effect was confirmed by inhibition of the PI3K/Akt downstream cytosolic signaling pathway,” the researchers wrote.

Using antibodies to block ApoA1 from physically interacting and being incorporated into mBECs also increased cell death, suggesting that ApoA1 needs to interact and be taken up by cells in order to exert its protective effects.

More lab experiments

Additional experiments showed that growing mBECs in a dish containing cells that produced and released ApoA1, called hBM-EPCs, also had protective effects on mBECs.

“These findings provide evidence that ApoA1 may be a potential novel therapeutic agent for protection of the endothelium in ALS by reducing cell death induced by the pathologic environment via protein incorporation into cells,” the researchers wrote.

The team noted that more research is needed to validate these findings, such as testing whether the same phenomena also are seen in living animal models.

“It’s a little early to predict what the ultimate effect is for patients,” said Alison Willing, PhD, a professor at USF and a study author. “In this study, we used a cell culture model where we can control all aspects of what the cells are exposed to. It is not possible to have the same degree of control in people.”

Professor Cesario Borlongan, PhD, is a co-investigator in this study.