Arteriosclerosis (2) and sulphation factor

The alpha granules of platelets contain many substances which are useful for repairing damaged tissue, especially damaged blood vessels. That's no surprise.

The addition of sulphate to sugar and sugar derived molecules is essential for the production of many glycosaminoglycans. Most of the work with sulphation has centred on cartilage development but an equally interesting location of sulphated GAG production is the arterial wall which leads to the formation of fibrous plaques, via proteoglycans, in stressed areas.

In ancient days of old Salmon and Daughaday (1957 from the look of this title) wanted to assay Growth Hormone. They developed GH deficient rats (better not ask how) then took cartilage samples and added GH to see if they could get sulphate uptake as a method of assaying GH levels in serum, a bioassay. The idea failed and they eventually found out that "Sulphation Factor" was needed for sulphate uptake and SF was produced in response to GH by the liver, GH per se was not active on isolated chondrocytes. To confuse matters further, at some stage SF was re named Somatomedin. To make matters even more confusing somatomedin was even later discovered to be ILGF-1. There is a nice summary of the story here.

Even today we still use ILGF-1 as a surrogate for measuring GH in cats with GH secreting tumours.

So the sulphation of proteoglycans is mediated through ILGF-1. A brief scan (Wiki) of the contents of alpha granules in platelets lists ILGF-1 as the first ingredient. Platelets deliver ILGF-1 to damaged areas. It's not exactly surprising that ILGF-1 promotes proteoglycan sulphation as well as, or as part of, tissue repair.

Human beings are not designed to have fasting insulin levels over 200pmol with a rise of up to 1000pmol (in extreme cases) post prandially. If we do things to ourselves which produce this effect we can expect to have insulin interacting of ILGF-1 receptors which were never designed to see such astronomical insulin levels. Even if their true ligand is at minimal concentration, arterial wall cells will behave as if platelets are delivering ILGF-1 in "damage repairing" amounts. Even in the absence of damage.

It does not take a great leap of faith to suggest that the normal physiological response to normal vascular injury might be driven beyond an appropriate level by chronic hyperinsulinaemia acting on ILGF-1 receptors.

Perhaps type two diabetics should be at increased risk of heart disease? I wonder if anyone has checked this...

Peter

BTW anyone who has followed the homocystine hypothesis of CVD will find the title (all I can get) of this paper of some interest.