HDL Elevation and Lipid Lowering Therapy: Current Scenario and Future Perspectives

Chhabria, Mahesh T.; Suhagia, Bhanubhai N.; Brahmkshatriya, Pathik S.

doi:10.2174/157489007782418973

Cited by 5 publications

(2 citation statements)

References 249 publications

(234 reference statements)

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“…HDL is known as “good cholesterol” given the inverse correlation between HDL levels and the incidences of cardiovascular disease. Until recently, raising circulating HDL levels has been thought of as a treatment for arteriosclerosis, while today increasing specific functional forms of HDL, and not just total HDL levels, is considered a more viable treatment (Joy and Hegele, 2008; Chhabria et al, 2007). Puzzling in this regard is that HDL particles upon lipidation form a wide range of shapes and sizes, with the ability to transform from lipid-poor globular proteins to discoidal and to spherical particles.…”

Section: Introductionmentioning

confidence: 99%

Maturation of high-density lipoproteins

Shih

Sligar

Schulten

2009

J. R. Soc. Interface.

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Human high-density lipoproteins (HDLs) are involved in the transport of cholesterol. The mechanism by which HDL assembles and functions is not well understood owing to a lack of structural information on circulating spherical HDL. Here, we report a series of molecular dynamics simulations that describe the maturation of discoidal HDL into spherical HDL upon incorporation of cholesterol ester as well as the resulting atomic level structure of a mature circulating spherical HDL particle. Sixty cholesterol ester molecules were added in a stepwise fashion to a discoidal HDL particle containing two apolipoproteins wrapped around a 160 dipalmitoylphosphatidylcholine lipid bilayer. The resulting matured particle, captured in a coarse-grained description, was then described in a consistent all-atom representation and analysed in chemical detail. The simulations show that maturation results from the formation of a highly dynamic hydrophobic core comprised of cholesterol ester surrounded by phospholipid and protein; the two apolipoprotein strands remain in a belt-like conformation as seen in the discoidal HDL particle, but with flexible N-and C-terminal helices and a central region stabilized by salt bridges. In the otherwise flexible lipoproteins, a less mobile central region provides an ideal location to bind lecithin cholesterol acyltransferase, the key enzyme that converts cholesterol to cholesterol ester during HDL maturation.

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Section: Introductionmentioning

confidence: 99%

Maturation of high-density lipoproteins

Shih

Sligar

Schulten

2009

J. R. Soc. Interface.

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“…There is now great interest in identifying new agents for raising HDL or for improving its function, with the expectation that a combined approach of simultaneously lowering LDL and raising HDL will be more effective in reducing cardiovascular events than only lowering LDL, which in most trials reduces clinical events by only approximately 30% [2–5]. Currently, the most effective drug for increasing HDL is niacin but its use has been limited because of side effects, although newer slower release formulations of niacin coupled with selective prostaglandin D2 receptor antagonists may ameloriate this problem [6].…”

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confidence: 99%