Tuesday, June 24, 2014

Further speculation on lipid deposition

Before I start, let me be clear that the following is clear speculations
but it is a speculation based on preliminary facts thats seems to
results from our understanding of gene behaviors and major clinical events.
The fact is we build up cholesterol or lipid Atheromas in the blood vessels
and that simple factleads to major devastating events which at time terminates our
life in terms of stroke or cardiac attacks.
It is worth examining the the build up of Atheromas in a more detail fashon if we intend
to make a difference.
Our current understanding is that at one time in our life, during the normal development,
the build up of Atheroma starts.  We are talking about lipid deposition in our arteries.
for Artery to receive and capture  fat molecules, there must be structures and potentially cells that
must be ready to receive them, and receive them tightly in order to hold them for what appears to be years at
a time.  We suspect that the chemical structure of Laminin, fibronectin, or fibrin or one of these structures(other will add Pectin, Perlectan,Entactin)
that we commonly deem "cellular environment" appears to hold on to lipid matters somewhat tighly relatively.
However, the capillary "cellular environment" over the years, is constantly undergoing a shift under hormones,
cytokine and various stresses. This shift in composition, ultimately impacts the very nature
of the underlying molecules, and therefore lipid to parietal molecule interactions, jeopardizing the tight neat
relation at lipid-laminin or lipid-elastin interaction.  It is clear that cytokines may chance the very nature
of "cellular environment" and changing so very drastically as, at cellular level, mutations or gene line shutdown could
follow changes in cytokine or ambiant hormonal milieu.
The very example of Menopause and the rise of cardiovascular events in women is a perfect example of this phenomenon. The disapearance of Estrogen during
menopause affects drastically this interaction marking a rise in coronary events in women (what stabilize this event should be a lesson for all to learn)
And the disapearance dwindeling of Elastin content in the composition of blood vessel with advancing age
appears to be another evidence of these changes that go completely unnoticed but clearly affect our future life!
The structural composition of laminin has long attracted the observation of scientists, indeed this molecule has
many locations where binding to specific structures is made easy, we speak of chemical bonds. And certain Ateromas may feel
confortable sitting here and tightly!  The point of the matter is that at any given location,
the cellular environment makes it possible for Atheroma seeding.  The perfect example is the disease called Xanthelasma or tuberous Xanthomas, this is a mere
deposition of lipids in a part of our body where for all suspicions must haVE A SPECIAL CELLULAR ENVIRONMENT that provide seeding of lipids.  I bet you those eyelids
have special laminin or fibronectin composition.
And it is clearly foolish to believe that fat deposition does not have consequences.  This is the same foolishnes that
made our leaders debate for long time that obesity was not a disease state.  Fat deposition has profound consequences because it
other directly induce reaction or secondarily provoke secondary effects...and my suspicion if a new burse of cytokines that
will induce the "disease state".   Clearly, the resulting Arthropathy is evidence of such reaction.  All chholesterol disturbances are linked to Arthropathies
as a result.
An interesting question being explored currently is the role of pericytes.  There is no no single pericytes,
and locally, at site of cholesterol deposition, the pericyte composition may be not the same as other locations.  And the pericyte type predominant
in an area of Atheroma may not be the same as an area of absent lipid deposition.  Scientist are digging deeper at gene level, this is where the nature of integrins
and G-proteins may also vary.  This point links us to why diabetic patients particularly present various levels of Vasulitic process, some ending in Amputations
and various leg wounds, and some none...clearly Integrins (alpha, Beta family) and G-proteins have something to do that is worth examining...And then there is PDGFR-beta, NG2 and gets more complex )
CRBCM is clearly with you in this path to knowledge...
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