Murine macrophage RAW264 were investigated for their response to lipid-free apolipoproteins. Preincubation of the cells with 300 microM dibutyryl cyclic (dBc) AMP for 16 h induced specific binding of apolipoprotein (apo) A-I to the cells and apoA-I-mediated HDL formation with cellular lipids, neither of which was detected in the absence of dBcAMP. Dose-dependent changes of the apoA-I specific binding and the apoA-I-mediated cholesterol release were largely superimposable. ApoA-II also mediated lipid release after the treatment of the cells with dBcAMP and effectively displaced the apoA-I binding to the cells. In contrast, cellular cholesterol efflux to lipid microemulsion and to 2-(hydroxypropyl)-beta-cyclodextrin was uninfluenced by the dBcAMP treatment. To induce the cellular reactivity with apoA-I, the incubation with dBcAMP required at least 6 h. Actinomycin D, cycloheximide, puromycin, and brefeldin A suppressed both the induction of apoA-I-mediated lipid release and the apoA-I specific binding to the cells. Analysis of the expression level of ABC1 mRNA by using reverse transcription-polymerase chain reaction and oligonucleotide arrays revealed that ABC1 mRNA was already expressed in the dBcAMP-untreated cells, and the dBcAMP treatment for 16 h enhanced its expression 9-13-fold. We conclude that dBcAMP selectively induces apolipoprotein-mediated cellular lipid release and accordingly high-density lipoprotein generation by inducing specific binding of apolipoprotein, but does not influence diffusion-mediated lipid efflux. The cell-apolipoprotein interaction seems to depend on cellular protein biosynthesis and transport. A substantial increase in the level of ABC1 mRNA caused by the dBcAMP treatment indicates that ATP-binding cassette transporter 1, the protein product of ABC1, may directly be responsible for the interaction, but the question about the absence of the interaction with its baseline expression level remains.

Expression of ATP binding cassette transporter A1 (ABCA1), a major regulator of high density lipoprotein (HDL) biogenesis, is known to be up-regulated by the transcription factor liver X receptor (LXR) α, and expression is further enhanced by activation of the peroxisome proliferator activated receptors (PPARs). We investigated this complex regulatory network using specific PPAR agonists: four fibrates (fenofibrate, bezafibrate, gemfibrozil and LY518674), a PPAR δ agonist (GW501516) and a PPAR γ agonist (pioglitazone). All of these compounds increased the expression of LXRs, PPARs and ABCA1 mRNAs, and associated apoA-I-mediated lipid release in THP-1 macrophage, WI38 fibroblast and mouse fibroblast. When mouse fibroblasts lacking expression of PPAR α were examined, the effects of fenofibrate and LY518674 were markedly diminished while induction by other ligands were retained. The PPAR α promoter was activated by all of these compounds in an LXR α-dependent manner, and partially in a PPAR α-dependent manner, in mouse fibroblast. The LXR responsive element (LXRE)-luciferase activity was enhanced by all the compounds in an LXR α-dependent manner in mouse fibroblast. This activation was exclusively PPAR α-dependent by fenofibrate and LY518674, but nonexclusively by the others. We conclude that PPARs and LXRs are involved in the regulation of ABCA1 expression and HDL biogenesis in a cooperative signal transduction pathway.

hile coronary perforation is an uncommon complication following percutaneous coronary intervention (PCI), [1][2][3][4][5][6][7][8] it is one that may lead to cardiac tamponade, 6-9 emergency coronary artery bypass surgery (CABG), or pseudoaneurysm formation, 10 with the potential for late coronary rupture. New coronary devices that resect (eg, directional or transluminal extraction atherectomy), ablate (eg, rotational atherectomy or excimer laser angioplasty), or score (eg, the cutting balloon) atherosclerotic plaque may increase the risk of coronary perforation, and a number of angiographic risk factors for its occurrence have been described previously. [11][12][13][14] The use of newer higher-weight and hydrophilic coronary guidewires may also increase the risk of coronary perforation, particularly during the treatment of chronic coronary occlusions. Clinical algorithms for the treatment of coronary perforation based on angiographic and clinical criteria have been Circulation Journal Vol.66, April 2002 less well studied. Moreover, descriptions of the long-term sequelae after coronary perforation, and delineation of the potential risk for late pseudoaneurysm formation and coronary rupture, have been lacking.The present study examines the frequency of coronary perforation during PCI, evaluates the management strategies used to treat the perforation, and describes the long-term prognosis in patients who have developed coronary perforation during PCI. To address these issues, we reviewed our experience with coronary perforation in a consecutive series of 7,443 patients undergoing PCI at a single, highvolume clinical center. Methods Patient PopulationBetween January 1992 and December 1996, 7,443 coronary interventional procedures were performed in the Cardiac Catheterization Laboratory at National Toyohashi Higashi Hospital. These procedures included conventional balloon angioplasty (n=4,895; 65.8%), cutting balloon angioplasty (n=1,274; 17.1%), coronary artery stenting (n=810; 10.9%), directional coronary atherectomy (DCA) (n=440; 5.9%), and transluminal extraction catheter atherectomy (n=24, 0.32%). Coronary perforation is a rare but serious complication that occurs during percutaneous coronary intervention (PCI). This study examines the frequency of coronary perforation during PCI, evaluates the management strategies used to treat perforations, and describes the long-term prognosis of patients who have developed coronary perforation during PCI. Coronary perforations were found in 69 (0.93%) of 7,443 consecutive PCI procedures, occurring more often after use of a new device (0.86%) than after use of balloon angioplasty (0.41%) (p<0.05).Coronary perforation was attributable solely to the coronary guidewire in 27 (0.36%) cases. Coronary perforations were divided into 2 types: (1) Those with epicardial staining without a jet of contrast extravasation (type I, n=51), and (2) those with a jet of contrast extravasation (type II, n=18). Patients with type I and type II perforations were managed by observation only (3...