|
Seminar
2
Date: February 6, 2008,
4:00 - 5:00 pm
Location: Gerstenzang 121, Brandeis University,
Waltham, MA
"Discrete roles of apoA-I and apoE in the biogenesis
of HDL species: Lessons learned from adenovirus-mediated gene
transfer in apoA-I-deficient mice." [view
recording of presentation>>]
Dr. Vassilis Zannis,
Ph.D. , Professor of Biochemistry, Departments of Medicine
and Biochemistry, Boston University School of Medicine, Boston,
MA
Abstract:
Using adenovirus-mediated gene transfer in apoA-I-deficient
mice, we have established that apoA-I mutations inhibit discrete
steps in a pathway that leads to the biogenesis and remodeling
of HDL. To this point, five discrete categories of
apoA-I mutants have been characterized that may affect the
interactions of apoA-I with ABCA1 or LCAT or may influence
the plasma PLTP activity or may cause various forms of dyslipidemia.Biogenesis
of HDL is not a unique property of apoA-I. Using adenovirus-mediated
gene transfer of apoE in apoA-I- or ABCA1-deficient mice,
we have established that apoE also participates in a novel
pathway of biogenesis of apoE-containing HDL particles. This
process requires the functions of the ABCA1 lipid transporter
and LCAT and it is promoted by substitution of hydrophobic
residues in the 261 to 269 region of apoE by Ala.The apoE-containing
HDL particles formed in the circulation may have atheroprotective
properties. ApoE-containing HDL may also have important biological
functions in the brain that confer protection from Alzheimer’s
disease.
Citations:
- Angeliki Chroni, Adelina Duka,
Horng-Yuan Kan, Tong Liu, and Vassilis I. Zannis, Point
Mutations in Apolipoprotein A-I Mimic the Phenotype Observed
in Patients with Classical Lecithin:Cholesterol Acyltransferase
Deficiency, Biochemistry 2005, 44, 14353-14366
- Varvara Nikolaidou-Neokosmidou,
, Vassilis I. Zannis and Dimitris Kardassis, Inhibition
of hepatocyte nuclear factor 4 transcriptional activity
by the nuclear factor kB pathway, Biochem. J. (2006)
398, 439–450 (Printed in Great Britain)
- Kyriakos E. Kypreos and Vassilis
I. Zannis, Pathway
of biogenesis of apolipoprotein E-containing HDL in vivo
with the participation of ABCA1 and LCAT, Biochemical
Journal, (2007) 403, 359–367(Printed in Great Britain)
Seminar 1
Date: October 3, 2007, 4:00 - 5:00
pm
Location: Gerstenzang 121, Brandeis University,
Waltham, MA
"Diet and Heart Disease: The Seven Countries
and Beyond" [view presentation
slides>>]
Dr. Walter
C. Willett, M.D., Dr. P.H., Harvard University Medical
School, Boston, MA
Abstract:
Studies of different populations worldwide and of migrants
from low- to high-risk regions indicate that coronary heart
disease (CHD) is potentially almost entirely preventable.
Mechanistic studies during the last decade have indicated
that many biological pathways can lead to CHD, and the opportunities
for prevention have thus been expanded.
Smoking accounts for about one third of myocardial
infarctions in Western countries, and overweight and obesity
contribute similarly. Reducing intake of total fat as a percent
of calories is not an effective means for prevention, but
multiple lines of evidence indicate that the type of dietary
fat has a major impact on risk of CHD. Intake of trans fat
from partially hydrogenated vegetable oils most strongly increases
the risk, saturated fat is weakly associated with greater
risk, monounsaturated fats moderately decrease risk, and polyunsaturated
fats strongly decrease risk. Both N-6 and N-3 polyunsaturated
fatty acids contribute to lower risk. The form of dietary
carbohydrate also appears to influence risk of CHD importantly;
highly refined starches are related to increased risk, but
consumption of whole-grain, high-fiber cereal products have
consistently been associated with lower risks. Higher consumption
of fruits and vegetables contributes to lower risk, probably
by multiple mechanisms. Many issues remain to be settled,
including the optimal mix of mono- and polyunsaturated fatty
acids, the optimal amounts of N-3 and N-6 fatty acids, the
amount and source of protein, and the effects of antioxidants,
other phytochemicals and minerals. From our long-term studies,
we have calculated that modest dietary changes, together with
avoidance of smoking, regular physical activity, and maintenance
of a healthy body weight can reduce rates of coronary heart
disease by over 80%. Failure to take advantage of dietary
and lifestyle means of preventing these diseases represents
a tremendous lost opportunity for improved health and wellbeing.
Citations:
|