A network-based approach to associate High Density Lipoprotein (HDL)''s subspeciation with its cardiovascular protective functions
Jingyuan Deng · OhioLink ETD Center (Ohio Library and Information Network) · 2012
High density lipoproteins are a heterogeneous group of particles composed of proteins and lipids that in approximately equal mass.The most abundant HDL proteins are apolipoprotein (apo) A-I and A-II, yet recent proteomic studies have identified up to 50 additional proteins within HDL.HDL is well-known for its critical cardiovascular disease (CVD) prevention function, which is mainly achieved through the mediation of the reverse cholesterol transport (RCT).In addition to that, recent studies have shown that HDL also displays a series of similarly diverse functions related with CVD-protection, including anti-oxidation, anti-inflammation, and endothelial relation.What"s more, a growing body of evidence (including our research) has suggested these diverse HDL functions may be mediated by distinct stable subspecies that happen to cofractionate with classically defined "HDL".To better characterize the structural composition and functionality of HDL subspecies, our collaborator have applied three non-density based orthogonal separation chromatography techniques (Gel filtration (GF), Anion exchange (AE), and Isoelectric focusing (IEF)) for the isolation of HDL from human plasmas.Generally, these techniques fractionated normal human plasmas to phospholipid-containing subfractions, then the HDL associated proteins and their distributions were determined using Mass Spectrometry.Given the proteomic profiles of HDL proteins, our work is to systematically identify the structural HDL subspecies and study their biological functions.In the first step, we assume that HDL associated proteins, which have similar co-migration patterns when separated by different techniques, are likely to form distinct lipoprotein subspecies.So for a protein pair, showing consistently high similarity in migration patterns across techniques would provide the strongest evidence of their co-existence in the same First, I would like to acknowledge my gratitude to my advisor and mentor Dr. Long (Jason) Lu, for all the valuable supervision, motivation and opportunities in the lab throughout my graduate studies.His willingness, high expectations and encouragement empower me with the knowledge and confidence to engage in my own pursuits.I deeply value Jason"s respect for his students" independence and interest as a regular person in addition to being budding scientists.I am very appreciating and grateful for all the training with him, and I am quite sure that without his care, supervision and friendship, I would not be able to complete this work.The next, I would like to express my sincere gratitude to my committee, Dr. Davidson Sean, Dr. Jarek Meller and Dr. Rao Marepalli, for their time and efforts in providing support and guidance throughout the duration of this thesis, and especially for their insightful advice and useful suggestions as well as encouragements in our committee meetings.I also would like to