Effects of stimulants and HIV Proteins on Pyroptosis and Apoptosis Pathways in Human Brain Microvascular Endothelial (hBMVEC)

Abstract

Human brain microvascular endothelial cells (hBMVEC), together with astrocytes and pericytes, construct the blood‐brain barrier (BBB) to protect the brain from toxins and pathogens via paracellular, transcellular, transporter, and extracellular matrices, and tight junction proteins. The BBB also inhibits many therapeutic substances from entering the brain, making it challenging to design drugs that can migrate through the BBB effectively. The objective of the project was to understand the detrimental effects of psychological stimulants (cocaine, THC, Amphetamine) and HIV Tat proteins on the integrity of the BBB, and to inform the potential therapeutic strategies. The hBMVEC cell culture was treated with the stimulants and two different constructs of HIV Tat proteins. Western blot and RT‐qPCR techniques were used to detect pyroptosis and apoptosis proteins that could lead to endothelial cell death. We found that proteins involved in apoptosis (PEA‐15, caspase‐3, and caspase‐8) were more expressed and upregulated comparing to proteins involved in pyroptosis (caspase‐1, gasdermin D) and cytokine proteins (IL‐1β, IL‐6, IL‐18).