{'fraction_non_alphanumeric': 0.02666666666666667, 'fraction_numerical': 0.003870967741935484, 'mean_word_length': 6.027190332326284, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Journey Through Cholesteryl Ester Transfer Protein Inhibition: From Bench to Bedside

High-density lipoprotein (HDL) possesses antiatherogenic properties that include reverse cholesterol transport (RCT), maintenance of endothelial function, and protection against thrombosis.1,2 The concentration of HDL is largely determined by the cholesteryl ester transfer protein (CETP) that decreases the ratio of HDL-cholesterol (HDL-C) over low-density lipoprotein-cholesterol (LDL-C). In this review, we will discuss the rationale and effectiveness of using HDL as a therapeutic target, by reducing CETP activity, as a means of cardiovascular morbidity reduction.

### Metabolism and Pathophysiology

HDL has been proposed to have several antiatherogenic properties that include the ability to mediate cholesterol efflux from macrophages, antioxidant capacity, anti-inflammatory properties, nitric oxide–promoting activity,1,2 and the ability to transport proteins with their own intrinsic biological activities.3 The steps describing the removal of excess cholesterol from macrophages to ultimate disposition in the feces are collectively known as RCT and are schematically summarized in Figure.4 Small nascent HDL particles composed of phospholipids and apolipoproteins (apo) are synthesized mainly in the liver and the intestine. These particles obtain additional apolipoproteins, free and esterified cholesterol, and excess phospholipids from chylomicrons and very LDL (VLDL) during their lipolytic conversion into triglyceride-depleted remnants. Free cholesterol is also acquired from peripheral tissues. HDL-associated apolipoproteins, including apoAI, play a central role in this process, serving as a signal transduction protein to mobilize cholesteryl esters (CEs) from intracellular pools. Of similar importance are ATP-binding cassette transporters A1 and ATP-binding cassette transporters G1 proteins expressed on the macrophage cell surface that mediate the transfer of cellular unesterified cholesterol to nascent discoidal and maturating globular HDL.5 The accepted cholesterol in HDL is subsequently transformed into CE by lecithin cholesterol acyl transferase, an enzyme that is also activated primarily by apoAI. Subsequently, HDL can transport its CE back to the liver via interaction with the scavenger receptor …