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I believe that the main paper this month is sufficiently important to quote the
abstract in full length.
1. Angiotensin II promotes atherosclerotic lesions and aneurysms in
apolipoprotein
E-deficient mice.
Daugherty A, Manning MW, Cassis LA
J Clin Invest 2000 Jun;105(11):1605-12
Division of Cardiovascular Medicine, Gill Heart Institute, Department of
Physiology, College of Pharmacy, University of Kentucky, Lexington, Kentucky
40536, USA. adaugh@pop.uky.edu
Increased plasma concentrations of angiotension II (Ang II) have been
implicated
in atherogenesis. To examine this relationship directly, we infused Ang II or
vehicle for 1 month via osmotic minipumps into mature apoE(-/-) mice. These
doses of Ang II did not alter arterial blood pressure, body weight, serum
cholesterol concentrations, or distribution of lipoprotein cholesterol.
However,
Ang II infusions promoted an increased severity of aortic atherosclerotic
lesions. These Ang II-induced lesions were predominantly lipid-laden
macrophages
and lymphocytes; moreover, Ang II promoted a marked increase in the number of
macrophages present in the adventitial tissue underlying lesions. Unexpectedly,
pronounced abdominal aortic aneurysms were present in apoE(-/-) mice infused
with Ang II. Sequential sectioning of aneurysmal abdominal aorta revealed two
major characteristics: an intact artery that is surrounded by a large remodeled
adventitia, and a medial break with pronounced dilation and more modestly
remodeled adventitial tissue. Although no atherosclerotic lesions were visible
at the medial break point, the presence of hyperlipidemia was required because
infusions of Ang II into apoE(+/+) mice failed to generate aneurysms. These
results demonstrate that increased plasma concentrations of Ang II have
profound
and rapid effects on vascular pathology when combined with hyperlipidemia, in
the absence of hemodynamic influences.
PMID: 10841519, UI: 20300769
Comment by mdt: The interested reader will have to
study the paper carefully and decide for him or
herself whether these lesions are really fusiform
abdominal aortic aneurysms. The gross specimen
shown in Figure 5 certainly looks like a AAA. But,
there is a problem with the histopathology. Two
lesions are described in the text and illustrated in
Figure 6. I will call them lesions A and B.
Quoting the authors: Lesion A "had intact elastin
layers in the media that were associated with
pronounced remodeling of the adventitial space. The
cross-sectional area of the lumen of the abdominal
aorta...was similar to that of tissues of the same
region from mice not infused with Ang II". IMHO,
without dilation of the lumen, I couldn't call it a
AAA.
Lesion B "was characterized by a complete medial
break that resulted in marked dilation of the
lumen." Well, that is not a typical AAA either,
although lumen and adventitia are both dilated. I
have never seen a human AAA that looked like that,
unless it were an aneurysm associated with an aortic
dissection. The typical AAA does have degenerative
changes in the media, but it is generalized and not
focal.
So, dear reader, you probably know that I would not
likely take a totally unopinionated view of this
subject, so you will have to look at the pictures
and decide for yourself.
On to the question of whether apoE genotypes are
important in human AAA.
2. Gerdes LU, Lindholt JS, Vammen S, Henneberg EW,
Fasting H. Apolipoprotein E genotype is associated
with differential expansion rates of small AAAs.
Br. J. Surg 2000; 87: 760-5.
Brief summary: Apo E genotypes were determined in 57
men with small AAAs (3-5 cm). Each had at least two
ultrasound exams over the next 2 - 4.5 years.
Results:
mm expansion/year # of subjects
E3/E4 1.3 17
E3/E3 2.1 31
E2/E3 3.1 6
E2/E4 4.2 3
comment by mdt: So, apoE genotype does influence
expansion rate of AAA, but in the wrong direction,
since the E2/E3 and E2/E4 groups are supposed to be
relatively protected from atherosclerosis.
3. Ilveskoski E, et al. Apolipoprotein E
polymorphism and carotid artery intima-media
thickness in a random sample of middle-aged men.
Atherosclerosis 2000; 153: 147-53.
Very Brief summary: A random sample of 189 Finnish
men were studied by ultrasound for IM ratio. The IM
ratio was lowest in men of the E3/2 genotype, and
the authors conclude that the E3/2 genotype is a
protective factor for carotid atherosclerosis,
perhaps because of its effect on lowering serum
cholesterol.
Comment by mdt: It should be interesting to compare
the distribution of genotypes among these normal
subjects and the aneurysm subjects described in the
other paper.
Normal AAA Normal AAA
3/3 109 31 55% 58%
2/3 20 6 11% 11%
2/4 or 3/4 60 19 34% 32%
------ -----
189 57
So, it looks like distribution of apoE alleles in
AAA patients strongly resembles the distribution in
a normal male population.