Korean Circ J.  2020 Mar;50(3):236-247. 10.4070/kcj.2019.0195.

Novel Associations between Related Proteins and Cellular Effects of High-Density Lipoprotein

Affiliations
  • 1Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea. shl1106@yuhs.ac
  • 2Center for Theragnosis, Biomedical Research Institute, Korean Institute of Science and Technology, Seoul, Korea. jelee9137@kist.re.kr
  • 3Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
  • 4Department of Chemistry, Sookmyung Women's University, Seoul, Korea.
  • 5Proteometech Inc., Seoul, Korea.
  • 6Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
  • 7KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul, Korea.
  • 8Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, Korea.

Abstract

BACKGROUND AND OBJECTIVES
Recent studies have examined the structure-function relationship of high-density lipoprotein (HDL). This study aimed to identify and rank HDL-associated proteins involved in several biological function of HDL.
METHODS
HDLs isolated from 48 participants were analyzed. Cholesterol efflux capacity, effect of HDL on nitric oxide production, and vascular cell adhesion molecule-1 expression were assessed. The relative abundance of identified proteins in the highest vs. lowest quartile was expressed using the normalized spectral abundance factor ratio.
RESULTS
After adjustment by multiple testing, six proteins, thyroxine-binding globulin, alpha-1B-glycoprotein, plasma serine protease inhibitor, vitronectin, angiotensinogen, and serum amyloid A-4, were more abundant (relative abundance ratio ≥2) in HDLs with the highest cholesterol efflux capacity. In contrast, three proteins, complement C4-A, alpha-2-macroglobulin, and immunoglobulin mu chain C region, were less abundant (relative abundance ratio <0.5). In terms of nitric oxide production and vascular cell adhesion molecule-1 expression, no proteins showed abundance ratios ≥2 or <0.5 after adjustment. Proteins correlated with the functional parameters of HDL belonged to diverse biological categories.
CONCLUSIONS
In summary, this study ranked proteins showing higher or lower abundance in HDLs with high functional capacities and newly identified multiple proteins linked to cholesterol efflux capacity.

Keyword

Atherosclerosis; Cardiovascular diseases; Proteomics; Lipoproteins; Immunity

MeSH Terms

Amyloid
Angiotensinogen
Atherosclerosis
Cardiovascular Diseases
Cholesterol
Complement System Proteins
Immunoglobulin mu-Chains
Lipoproteins*
Nitric Oxide
Plasma
Proteomics
Serine Proteases
Thyroxine-Binding Globulin
Vascular Cell Adhesion Molecule-1
Vitronectin
Amyloid
Angiotensinogen
Cholesterol
Complement System Proteins
Immunoglobulin mu-Chains
Lipoproteins
Nitric Oxide
Serine Proteases
Thyroxine-Binding Globulin
Vascular Cell Adhesion Molecule-1
Vitronectin

Figure

  • Figure 1 Results of each functional parameter of HDL according to quartile groups. Values of cholesterol efflux capacity (A), NO production (B), and VCAM-1 expression (C). HDL = high-density lipoprotein; NO = nitric oxide; VCAM = vascular cell adhesion molecule.

  • Figure 2 Proteins ranked by their differential abundance in HDL with high cholesterol efflux capacity. The ranking was determined by the NSAF ratio, which is log2-transformed in the figure. HDL = high-density lipoprotein; NSAF = normalized spectral abundance factor.

  • Figure 3 Proteins ranked by their differential abundance in HDL inducing high NO production. Ranking was determined by NSAF ratio, which is log2-transformed in the figure. HDL = high-density lipoprotein; NO = nitric oxide; NSAF = normalized spectral abundance factor.

  • Figure 4 Proteins ranked by their differential abundance in HDL inducing high VCAM-1 expression levels. Ranking was determined by NSAF ratio, which is log2-transformed in the figure. HDL = high-density lipoprotein; NSAF = normalized spectral abundance factor; VCAM = vascular cell adhesion molecule.


Cited by  1 articles

The Long and Winding Road: To the Proper Understanding of High-density Lipoprotein
Jidong Sung
Korean Circ J. 2020;50(3):248-249.    doi: 10.4070/kcj.2020.0020.


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