CYTOKINE REGULATION OF CHOLESTEROL TRAFFICKING

Project: Research project

Description

Atherosclerosis is the major cause of morbidity and mortality in the United
States. Plasma levels of LDL and cholesterol are major risk factors to its
development. In humans, the liver primarily controls plasma LDL and
cholesterol levels through LDL receptor-mediated catabolism and
cholesterol/lipoprotein biosynthesis. The milieu of the atherosclerotic
plaque, enriched with cytokines and growth factors, may be the key to
unravelling and controlling atherosclerosis. The goals of this research
project are to define at the cellular and molecular level the role of
microenvironment derived soluble mediators in regulating receptor-dependent
and independent uptake, synthesis, and accumulation of cholesterol at the
vessel wall, as well as systemically, in a hepatoblastoma-derived cell
line. The mechanisms regulating functional activity and gene expression of
the LDL receptor, scavenger receptor, and HMG-CoA reductase enzyme will be
defined in the cells comprising the atherosclerotic plaque and correlated
with SMC and macrophage cholesterol accumulation. Key mediators of
vascular cholesterol trafficking will be compared to inflammatory and
vascular cell-derived cytokine regulation of liver cholesterol metabolism.
Understanding, and thus ultimately coordinating vascular cell cholesterol
physiology with liver cholesterol catabolism is the long-term aim.
StatusFinished
Effective start/end date7/1/926/30/98

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $61,155.00

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Cholesterol
Cytokines
LDL Receptors
Liver
Atherosclerosis
Hepatoblastoma
Hydroxymethylglutaryl CoA Reductases
Scavenger Receptors
Atherosclerotic Plaques
Blood Vessels
LDL Cholesterol
Intercellular Signaling Peptides and Proteins
Lipoproteins
Macrophages
Morbidity
Gene Expression
Mortality
Enzymes

ASJC

  • Medicine(all)