The constituents of highly active anti-retroviral therapy (HAART) include HIV-1 
protease inhibitors (HPIs) and nucleoside reverse transcriptase inhibitors 
(NRTIs). Endothelial cell (EC) barriers, especially the blood-brain-barrier 
(BBB) suppresses the entry of HAART drugs to subendothelial HIV-1 reservoirs. 
The ATP binding cassette (ABC) transporter family members, multidrug resistant-1 
(MDR-1) and multidrug resistance-associated proteins (MRPs) can efflux both HPIs 
and NRTIs from intracellular compartments. Using brain derived ECs from 
non-human sources, previous studies suggested a dominant role for MDR-1 in HAART 
efflux from the BBB. However, due to species variations in ABC-transporter 
expression, drug-efflux functions using human brain ECs need to be investigated. 
Furthermore, roles of ABC-transporters in drug-efflux from systemic EC barriers 
need to be studied. We monitored the expression of ABC-transporters in primary 
human ECs obtained from brain (HBMVECs), aorta (HAECs), pulmonary-artery 
(HPAECs), dermal-microvessel (HDMVECs) and umbilical vein (HUVECs). Gene 
expression for MDR-1 and MRPs (MRP-1 to MRP-5) were analyzed by reverse 
transcriptase polymerase chain reaction (RT-PCR). Drug efflux functions were 
determined by calcein retention assays. Intracellular accumulation of both 
3H-saquinavir (an HPI) and 3H-zidovudine (an NRTI) were also monitored in HAECs 
and HBMVECs. Both assays were carried out in presence of verapamil (20-60 
microM) or MK-571 (12.5-50 microM) inhibitors of MDR-1 and MRPs, respectively in 
presence of verapamil or MK-571. The HBMVECs expressed higher levels of MRPs 
than MDR-1 and only MK-571 significantly (P<0.01) suppressed calcein efflux from 
these cells. However, both HAECs and HPAECs showed MDR-1 and MRP expression and 
calcein efflux was inhibited by both verapamil and MK-571. Both inhibitors 
suppressed 3H-saqubinavir efflux from HAECs, but only MK-571 suppressed 
saquinavir efflux from HBMVECs. In both ECs, 3H-zidovudine efflux was only 
suppressed by MK-571. Thus, primary human ECs, especially brain derived ECs, 
predominantly express MRPs and their specific inhibition may enhance HAART 
efficacy in subendothelial HIV-1 reservoirs.