Atherosclerosis and greasy sewer lines
is a story about one small town having to spend a quarter of a million
dollars a year clearing household grease from sewer lines. I bet it is true
everywhere. And with the holiday cooking season about to begin, cities know
the grease problem is heaviest this time of year.
am a specialist in microcirculation, inflammation, white cell rolling and
sticking, thrombosis and hemostasis. It wasn't long time ago when
endothelial cells were looked upon as wallpapers of the vasculature and
today they are communicating and helping to orchestrate the behaviour of all
our circulating cells.
support all the statements made by Kilmer “illustrative of the common
misconception of the pathogenesis of the atherosclerosis” and I can also
support your statement of early endothelial damage - but not always followed
by thrombus formation – sometimes of course there can be overstimulation
and a thrombus formed.
general response to an endothelial damage is activation of platelets but
also of all the inflammatory cells (that are called upon to come and repair
– and for the repair mainly the monocytes).
“rusty deposits” that Kilmer mentions are also triggering monocytes,
like oxidized cholesterol and LDL and products from Homocysteine that
Kilmer can describe better!
the leukocytes arrive and the monocytes, the inflammation starts and when
monocytes are activated they stimulate smooth muscle proliferation by all
the growth factors (among them basic Fibroblast Growth Factor - bFGF) which
are the basic events in atherosclerosis and the thickening of the wall.
you know, what Kilmer told me that if you remove the cholesterol oxides from
the cholesterol (you by from Sigma) you can inject any amount into animals
without any deposits forming in the aorta. Right Kilmer?
- So the oxidized stuff is the culprit –
stimulating and activating the inflammatory cells. You may also know
that activated “white cells” generate a lot of free radicals that make
further damage and release myeloperoxidase and carry on the inflammation.
activated inflammatory cells are present and generating and releasing free
radicals they also release MPO (myeloperoxidase). This can be seen as a sign
of low grade inflammation
the October 23 issue of New England J of Med (2003;349:1595-1604) there was
an interesting article:
Value of Myeloperoxidase in Patients with Chest Pain
am pretty sure Kilmer will support this from his experience in
other time I could tell you more about why smoking is so damaging and
creating atherosclerosis and from experiments
why scavenging the radicals with Vitamin C would be so helpful when
free radicals are inhaled with the smoke.
you seen the interesting study in
New England J Med Nov. 29, 2001 ?
?Decreased Rate of Coronary Restenosis after Lowering of Plasma Homocysteine Levels (this paper is attached). It is not easy to make a study where you in a time period of one year can document that taking three vitamins B6, B12 and Folic acid will decrease restenosis most likely because of diminished Homocysteine levels.
please don’t forget that most antioxidants are there to prevent different
fats and cholesterol and LDL to become oxidized. When they are, they will
trigger the inflammatory cells to try and remove it and the cascades are
running. Most of your E-vitamin are associated with your LDL molecules.
additional point. The statins, which block the Q10 synthesis, (Q10 is a
necessary anti-oxidant in heart mitochondria) are in fact working also as
antiinflammatory (decreased binding of white cells to the endothelial lining)
this is described in the litterature. Statins
should not be used because of all side effects
this is complicated biology indeed because the different white cells are
doing a lot of other things including
also hunting down your tumor cells.
items listed when you search for statins
and inflammation and
I take the freedom to take one sentence out of context:
findings support the idea of non-lipid effects of statins in atherosclerosis.
Further, recent observations using in vivo and in vitro models of
atherosclerosis have shed light on their potential role for manipulation of
various cellular functions via inhibition of the mevalonate pathway. Among
them, recently identified inhibitory effects of statins on
monocyte-endothelial interaction suggest their effect on inflammation.
Herein, we discuss recent progress in this area of study, with special focus
on the biological function of statins.
to Osler atherosclerotic changes of the arteries are seen in syphilis and
typhoid fever, even in children, and focal arterial degeneration are found
in great frequency in children who have died from scarlet fever, measles,
diphtheria, smallpox and influenza (J Pathol. 12, 426, 1907)
and virus, or their DNA have been found by various techniques in the
atherosclerotic lesions in a large proportion of patients, in particular
Chlamydia pneumonia (the TWAR bacteria) and cytomegalovirus (too many papers
toxins and cytokines are seen more often in the blood from patients with
recent heart disease and stroke, in particular during and after an acute
cardiovascular event, and some of them are strong predictors of
cardiovascular disease (again, too
many papers to quote)
Acute infections, most often in the upper respiratory tract have been noted in a large proportion of patients 2-4 weeks before they are struck by a myocardial infarction or a stroke (Neurology 50, 196-203, 1998; J Intern Med 225, 293-296, 1989; Stroke 27, 1999-2004, 1996; BMJ 296, 1156-60, 1988). The frequency of infections in these patients is significantly higher than in appropriate control individuals.
is a strong association between infectious burden, expressed as number of
seropositive reactions against various microorganisms, and degree of
atherosclerosis and also risk of CV mortality (Circulation 1054, 15-21,
five trials treatment of patients with coronary heart disease with
antibiotics that are effective against Chlamydia pneumonia, was successful;
a total of 104 cardiovascular events were noted among the 412 non-treated
ts, but only 61 events among the 410 patients in the treatment groups.
(Lancet 350, 404-407, 1997. Circulation 96, 404-407, 1997. Circulation 102,
1755-1760, 2000. Circulation 106, 1219-1223, 2002. Circulation 105,
2646-2652, 2002). In one
further trial a significant decreased progression of atherosclerosis in the
carotid arteries was seen (Circulation 106, 2428-2433, 2002).
However, in four other trials, one of which included more than 7000 patients, no significant effect was seen (Circulation 99, 1540-1547, 1999. J. Med. Ass. Thailand 84 (Suppl 3), S669-S675, 2001. Lancet 361, 809-813, 2003. JAMA 290, 1459-1466, 2003).
reason for these inconsistent results may be that the treatment was too
short (in one of the trials treatment was only given for five days). Also,
Chlamydia pneumoniae, the TWAR bacteria, can only propagate inside human
cells and when located in white blood cells they are resistant to
antibiotics. Treatment may also have been ineffective because the mentioned
antibiotics have no effect on virus. In this connection it is interesting to
mention that vaccination against influenza
a viral disease prevented heart mortality; after six months 8 % of
the control patients had died, but only 2 % of the vaccinated patients (Circulation
105, 2143-2147, 2002). It is worth mentioning that this effect was much
better than that achieved by any statin trial, and in a much shorter time.
is difficult, at least for me, to dispel these findings with the idea that
the infections are secondary, that the microorganisms are innocent
bystanders. On the other side, to class atherosclerosis as an infectious
disease does not exclude important roles of other factors. Any compound
toxic to the arterial intima may predispose to attacks from microorganisms.
This creates considerable difficulty in demonstrating that a particular organism is the necessary, but insufficient cause of a disease. It seems to me that the presence of antibodies is a crude measure of whether a microbe is involved in a disease, yet so often this is what is measured. The best evidence is to attempt to eradicate the microbe or interfere with its pathogenic action, but any agent used for this purpose would have to be effective and selective for the purpose it was intended. Nevertheless, on current evidence, microbes are at least as attractive putative “causers” of atherosclerosis as any nutritional or psychological excess or lack.
re Kilmer's description of the arterio/athero sclerotic process. His first
words are "connective tissue changes" and NOT: white
cells,endothelium, inflammation, cell proliferation et al.
The causa causans
may well lie in the "ground substance" that cell containing fibrous
sponge like structure that determines what reaches and leaves the
cells they surround. The superb
book by Morrison and Schjeide "Coronary
Heart Disease and the Mucopolysaccharides (Glycosaminoglycans)"
[ISBN 0398029032; 1974] is a primer as to the role
of connective tissue and its sulfation [think homocysteine]. Once the ground
substance deteriorates or what it does, so do the cells,
be they endothelium or muscle or white cells.
Ground substance i.e.
connective tissue is closely related / made of: cartilage /chondroitinS /
glucosamine / sulfate / keratin / hyaluronic acid /heparinS et al.
re Morley's viral or bacterial microorganisms in atherosclerosis, I believe
his key word is "opportunistic".
I believe that the opportunity
for inflammation and damage manifests itself to a large degree
due to suboptimal micronutrient intake, i.e. low E, C, the B's, D,
omega-3 and the carotenoids that weaken the system and allow opportunity
for microorganisms getting out of hand.
For example, the role
of low selenium status in cardiomyopathy and in viruses getting the
opportunity of doing damage is well established.
Ergo: optimizing micronutrients will lower microorganism "opportunity", strengthen the host, decrease Kilmer's homocysteine thiolactone and maintain a happy ground substance, the very foundation of cell health and function. Micronutrients are the great confounder and we can beat ourselves silly over inflammation, cholesterol, carbs and stress if we don't first account for their role and status, with homocysteine our best marker to date.