Rationale: Hydrolysis of intracellular cholesterol ester (CE) is the key step in the reverse cholesterol transport in macrophage foam cells. We have recently shown that neutral cholesterol ester hydrolase (Nceh)1 and hormone-sensitive lipase (Lipe) are key regulators of this process in mouse macrophages. However, it remains unknown which enzyme is critical in human macrophages and atherosclerosis.Objective: We aimed to identify the enzyme responsible for the CE hydrolysis in human macrophages and to determine its expression in human atherosclerosis. Methods and Results:We compared the expression of NCEH1, LIPE, and cholesterol ester hydrolase (CES1) in human monocyte-derived macrophages (HMMs) and examined the effects of inhibition or overexpression of each enzyme in the cholesterol trafficking. The pattern of expression of NCEH1 was similar to that of neutral CE hydrolase activity during the differentiation of HMMs. Overexpression of human NCEH1 increased the hydrolysis of CE, thereby stimulating cholesterol mobilization from THP-1 macrophages. Knockdown of NCEH1 specifically reduced the neutral CE hydrolase activity. Pharmacological inhibition of NCEH1 also increased the cellular CE in HMMs. In contrast, LIPE was barely detectable in HMMs, and its inhibition did not decrease neutral CE hydrolase activity. Neither overexpression nor knockdown of CES1 affected the neutral CE hydrolase activity. NCEH1 was expressed in CD68-positive macrophage foam cells of human atherosclerotic lesions. A therosclerotic cardiovascular diseases are the leading cause of mortality in industrialized countries, despite advances in the management of coronary risk factors. Heart attacks arise from the thrombotic occlusion of coronary arteries following the rupture of plaques. Lipid-rich plaques, which are characterized by a plethora of cholesterol ester (CE)-laden macrophage foam cells, are prone to rupture. 1 Esterification of cholesterol in macrophages is mediated by acyl-coenzyme A cholesterol acyltransferase 1 or sterol Oacyltransferase 1 (SOAT1). 2 Conflicting results have been reported as to the effects of genetic ablation of SOAT1 on atherosclerosis in mice. 3,4 Furthermore, it has not been successful to demonstrate the efficacy of nonselective inhibitors of SOAT to clinically prevent the atherosclerosis in humans. 5,6 On the other hand, the hydrolysis of intracellular CE is the initial step of reverse cholesterol transport. 7 As the hydrolysis of CE preceding reverse cholesterol transport takes place at neutral pH, the enzymes catalyzing it have been collectively called neutral CE hydrolases. Because this step is rate-limiting, particularly in macrophage foam cells, 8,9 it is important to clarify the mechanisms that mediate the hydrolysis of CE in foam cells. Conclusions: NCEH1 is expressed in human atheromatousTo date, 3 enzymes have been proposed to serve as neutral CE hydrolases in macrophages: hormone-sensitive lipase (LIPE) 10 ; cholesteryl ester hydrolase (CEH), 11 which is identical to human liver carboxylesterase 1 ...

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Theinteraction offormicacid (HCOOH) with Pd(ll0) wasstudiedusing TPO and XPS. At low doses, at an adsorption temperature of 140 K, HCOOH decomposed to yield CO, COa, H2 and H20 during TPD. CO and Hz were evolved in desorption-limited peaks at 470 and 320 K, respectively. The CO and H z 0 desorptions were saturated at very low doses indicating only a small degreeof formate dehydration in such a transient experiment. The CO2 and Hz evolution continued to increase with dose and the CO2 evolved in a decompmition-limited peak a t 237 K a t low doses which broadened to lower temperature with increasing coverage. This dehydrogenation of HCOOH was of first order with an activation energy of 40 kJ mol-'. At doses above 0.5 L molecularly chemisorbed HCOOH was observed to desorb at 210 K and at still higher doses physisorbed multilayers were present and desorbed a t 180 K. XPS confvmed the presence of CO above 250 K and formate below this temperature. When oxygen was pre-dosed the formate was significantly stabilized and its coverage increased, the CO desorption was removed and Ha was produced a t higher temperatures a t the expense of the H2 peak at 320 K.