Pioglitazone enhances cholesterol efflux from macrophages by increasing ABCA1/ABCG1 expressions via PPARγ/LXRα pathway: Findings from in vitro and ex vivo studies

Beneficial Effects of Exercise-Based Cardiac Rehabilitation on High-Density Lipoprotein-Mediated Cholesterol Efflux Capacity in Patients with Acute Coronary Syndrome

“…Aerobic exercise has been shown to statins and niacin increase HDL cholesterol efflux capacity 14,17) . In contrast, studies including ours reported that treatment with pioglitazone, a peroxisome proliferator-activated receptor (PPAR ) agonist, resulted in a significant increases in HDL cholesterol efflux capacity in patients with metabolic syndrome and/or DM 14,18) . It was shown that PPAR agonist increased ATP-binding cassette A1 (ABC A1) in liver X receptor (LXR)-dependent manner, which resulted in enhanced cholesterol efflux capacity 18) .…”

“…In contrast, studies including ours reported that treatment with pioglitazone, a peroxisome proliferator-activated receptor (PPAR ) agonist, resulted in a significant increases in HDL cholesterol efflux capacity in patients with metabolic syndrome and/or DM 14,18) . It was shown that PPAR agonist increased ATP-binding cassette A1 (ABC A1) in liver X receptor (LXR)-dependent manner, which resulted in enhanced cholesterol efflux capacity 18) . In addition, our group reported that addition of telmisartan, a PPAR -activating angiotensin type 1 receptor blocker to cell cultures also increased ABC A1 and LXR in macrophage gene expression and enhanced cholesterol efflux capacity from THP-1 macrophages 19).…”

“…Therefore, not only exercise training, but comprehensive CR might affect the HDL cholesterol efflux capacity. Previous studies reported that PPAR agonists significantly increased HDL cholesterol efflux capacity 14,18) . In contrast, significant increases in HDL cholesterol efflux capacities were seen, irrespective of the taking pioglitazone and/or telmisartan in the CR patients.…”

“…Cholesterol efflux capacity was performed by experienced analysts at National Defense Medical College who were blinded to the clinical characteristics of the patients according to the methods used by Khera et al 12,14,[16][17][18][19][20] . J774 macrophages were purchased from RIKEN (Tsukuba, Japan), cultured in RPMI1640 medium containing 10% fetal bovine serum, and kept under constant conditions of 5% carbon dioxide and a temperature of 37 .…”

Relationship between Serum Cholesterol Efflux Capacity and Glucose Intolerance in Japanese-Americans

“…Briefly, THP-1 cells (Riken Cell Bank, Tsukuba, Japan) were maintained in RPMI 1640 (NikkenBio,Kyoto,Japan)containing10%fetalbovine serum. THP-1 cells were differentiated into macrophages with 320 nmol/l phorbol 12-myristate13-acetatefor72hours.Forthemeasurementofcholesterol efflux, the cells were cultured in a 24-well plate at a densityof1.0×10 6 cells/well.Themacrophageswere washed twice with phosphate buffered saline (PBS) and labeled via incubation in the presence of [ 3 H]-cholesterol(PerkinElmer,Boston,USA;finalconcentration 0.33 μCi/ml) in medium containing 0.2% bovine serum albumin (BSA) for 24 hours.The cells were washed twice with PBS containing 0.2% BSA andincubatedfor24hoursat37 ℃ inmediumcontaining0.2%BSAinthepresenceof0.5%serum(v/v) obtained from the study subjects as a cholesterol acceptor [25][26][27] .Followingincubation,thecultureswere centrifuged to remove cell debris, and the medium wasremovedtodeterminethelevelofradioactivity.At theendofthechaseperiod,themacrophagesweredissolved in a 3:2 (v/v) mixture of hexane/isopropanol, and the level of radioactivity per aliquot was measured.Thepercentageofcholesteroleffluxwascalculated by dividing the media-derived radioactivity by serum cholesterol efflux capacity was 32.6±5.7% in themenintheNGTgroup,31.6±6.0%inthemen intheIGTgroupand31.3±7.2%inthemeninthe DM group, compared to 33.6±6.4% in the women intheNGTgroup,31.0±6.4%inthewomeninthe IGTgroupand32.0±5.2%inthewomenintheDM group. In both sexes, the serum cholesterol efflux capacitytendedtobelowerinthesubjectswithIGT orDMthaninthosewithNGT,althoughthedifferencewasnotsignificant(P = 0.224formen,P = 0.062 forwomen).Inordertoexaminetheinfluenceofthe presenceofglucoseintolerance,wedividedthestudy subjects into an NGT group and glucose intolerance group.…”