IN VIVO-IN VITRO CORRELATES OF VASCULAR TOXICITY

Project: Research project

Description

The presence of toxic chemicals in various forms of
environmental pollution has been associated with an increase in
the extent and severity of vascular diseases. However, little is
known about the cellular and molecular mechanisms by which
specific vascular toxicants alter the structural and functional
integrity of the blood vessel wall. The present studies were
designed to test the hypothesis that exposure to allylamine and
benzo(a)pyrene, toxic environmental contaminants, result in the
phenotypic modulation of vascular smooth muscle cells. The
modulation of smooth muscle cells from a contractile to a
synthetic phenotype is in turn associated with enhanced cellular
proliferation and the formation of lesions that resemble those
found in atherosclerotic tissue. The effects of allylamine and
benzo(a)pyrene will be evaluated in atherosclerosis-susceptible
and non-susceptible animal classes. The structural integrity of
the vessels in situ will be evaluated after subchronic exposure to
the toxicants. Aortic smooth muscle cells obtained from control
or treated animals will be established in primary culture and
characterized by various morphological, biochemical and
functional criteria. Confluent cultures of smooth muscle cells in
the contractile state will be distinguished from synthetic cells by
their spindle shape and preponderance of myofilaments as
determined by light and electron microscopy. The synthetic and
proliferative capabilities of the cells will be evaluated by
measuring DNA and collagen synthesis using radiolabeled
substrates as a function to time in culture. The status of the
phosphoinositide system will be evaluated to determine if
alterations in turnover are correlated with enhanced
proliferative capacity. Cytoskeletal organization ornithine
decarboxylase activity and phosphoprotein profile will also be
evaluated. The responsiveness of smooth muscle cells to
angiotension II and norepinephrine will be examined as a function
of time to assess the functional status of the cells. The proposed
studies will provide information regarding the cellular
alterations associated with chemically-induced vascular injury.
Ultimately, this information can be used to better understand
the role that exposure to ubiquitous environmental contaminants
plays in the development of atherosclerosis and other
pathological changes of the vascular wall.
StatusFinished
Effective start/end date9/19/884/30/08

Funding

  • National Institutes of Health: $291,667.00
  • National Institutes of Health
  • National Institutes of Health: $236,844.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $91,742.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $288,000.00
  • National Institutes of Health: $293,666.00
  • National Institutes of Health: $132,457.00
  • National Institutes of Health: $294,000.00

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Smooth Muscle Myocytes
Blood Vessels
Atherosclerosis
Vascular Smooth Muscle
Aryl Hydrocarbon Receptors
Poisons
Allylamine
Carrier Proteins
Antioxidant Response Elements
Gene Expression
Vascular Diseases
Hydrocarbons
Aromatic Hydrocarbons
ras Genes
Genetic Promoter Regions
DNA
Artificial Cells
Oxidation-Reduction
Up-Regulation
Phenotype

ASJC

  • Environmental Science(all)
  • Medicine(all)