Spring 2006

The Milano Mutation

by Margaret Haffner

Limone sul Garda, according to many who visit it, is heaven on earth. Close your eyes and picture the setting - the beautiful lake, white sails dotting its azure waves, verdant mountains plunging to meet the lapping waters, pine trees whispering in the gentle breeze. Now, in your mind's eye, wander down the winding streets past gleaming white houses, admire the intricately formed wrought iron railings, the gates hiding who knows what private garden of Eden. Now sit at a bar in the piazza. Smell the fragrance of the flowers tumbling in colourful cascades from every balcony and planter. Sniff the tantalizing scents of rich spices, fresh baking and espresso coffee emanating from the shops on the perimeter of the piazza, and sip a glass of the robust vino locale. Who, you may ask, deserves to live in paradise?


For those of us who don't, live in paradise, that is, it is hard not to be a little jealous. Why aren't we so favoured? What did the citizens of Limone sul Garda do to deserve this slice of heaven? There has to be a down side, we tell ourselves. There must be a price to pay. Life can't be that good.


Or can it? What if, on top of all the above perks, you can eat and drink what you like - rich, fatty foods, cream, cheese, desserts - and not have to worry about heart disease? That is the case for some citizens of Limone sul Garda who are resistant to a common form of heart disease called atherosclerosis.


Enter the Milano Mutation. No, I'm not talking about some crazy mutation that turns people into big green hulks or web swinging crime fighters. This mutation turns people into walking medical miracles, and it is possessed by a lucky few in Limone sul Garda.


In our bodies, there are pesky bandit molecules called free radicals. Electrons, part of every atom, like to be in pairs (much like humans!), and each free radical has an unpaired electron.


So, instead of behaving in a civilized manner and putting up with their misfortune, these radicals steal electrons from unsuspecting healthy tissue such as artery walls. This causes the artery wall to become inflamed. Then LDH cholesterol (the evil twin of the good HDH cholesterol) moves into the openings in the artery wall caused by the inflammation. These LDH cholesterol molecules invite all their relatives to come and live with them. These squatters are the plaques that block the arteries.


So what does the Milano mutation do to fight off these squatters? First, we have to understand what happens in our bodies. We all have a protein called apolipoprotein A-I (apoA-I for short) which manufactures the good cholesterol whose role is to oust the evil twin. That's good! But frequently the evil twin's relatives are too numerous for HDH to get rid of and the plaques keep getting bigger and bigger. Enter apoA-I Milano, the mutant. ApoA-I Milano doesn't bother with trying to get rid of the squatters once they are there.


This superhero goes right to the heart of the problem and does battle with the free radicals themselves. Remember that the free radical tries to steal electrons from the artery wall in order to give its lonely electron a mate. Well, the apoA-I Milano turns the tables and steals the lonely electron for itself leaving the radical with all its electrons happily paired. Now the radical isn't radical anymore and is quite content to leave the artery wall alone. Therefore, there is nowhere for the LDH cholesterol to get a foot hold. No plaque, no atherosclerosis.


This is all very well and good for the lucky few people in paradise who have the mutation. Twenty years after it was first discovered, the carriers of this mutation are still free of cardiovascular disease. But is there help for the rest of us? As the understanding of how the mutation performs its miracle grows, researchers are confident that they will be able to use this knowledge to manufacture drugs which act like a combination of the normal and the mutated form of apoA-I, giving a one-two punch. These drugs will be able to round up the bad LDH cholesterol as well as inactivate the dangerous free radicals which start the disease process. So even we, who don't live in paradise, may in the near future be able to eat, drink and be merry without worry of heart disease.



Margaret Haffner is the author of two children's books as well as three murder mysteries. She works as a soybean biotechnologist with Agriculture Canada.



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