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Am J Cardiol. 2016 Oct 15;118(8):1187-1193. doi: 10.1016/j.amjcard.2016.07.035. Epub 2016 Jul 29.

Nonenzymatic Mechanism of Statins in Modulating Cholesterol Particles Formation.

Author information

1
Plaxgen Inc., Fremont, California. Electronic address: shan@plaxgen.com.
2
Plaxgen Inc., Fremont, California.
3
Stanford Shared FACS Facility, School of Medicine, Beckman Center, Stanford University, Stanford, California.
4
Molecular Medicine Research Institute, Sunnyvale, California.
5
Plaxgen Inc., Fremont, California; San Francisco General Hospital, University of California, San Francisco, California.

Abstract

Statin drugs are leading medication prescribed for treatment of dyslipidemic patients aimed at preventing both primary and secondary incidences of atherosclerosis-related cardiovascular events. Statin drugs competitively inhibit HMG-CoA reductase enzyme activity, thereby inhibiting cell-mediated cholesterol synthesis and reducing the low-density lipoprotein (LDL) cholesterol concentration of plasma. Conversely, the mechanism by which statins increase high-density lipoprotein (HDL) cholesterol concentration of plasma is not well understood. The plaque array method was used to examine the effect of statins on in vitro cholesterol particle formation. We observed that statins induced high-density cholesterol particle formation in buffer solution with or without the addition of human serum. Besides, simvastatin and lovastatin in their inactive pro-drug forms modulate formation of LDL and HDL cholesterol particles, indicating a novel nonenzymatic mechanism of statins. In a pilot study, screening of serum samples in the assay showed variation among patient samples in response to different statins. Specifically, screening of 50 serum samples with high cholesterol and statin treatment, compared with standard LDL-based measurement of statin efficacy, showed a good correlation for simvastatin (88%) and atorvastatin (84%). Taken together, our data indicate that statins, in addition to inhibiting enzyme-mediated cholesterol synthesis, have the capability to nonenzymatically modulate formation of LDL and HDL cholesterol particles in vitro. Similar interactions occurring in serum may provide a means to alter cholesterol particle formation in vivo.

PMID:
27614849
DOI:
10.1016/j.amjcard.2016.07.035
[Indexed for MEDLINE]

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