Too much clot  pg. 5

In the 1990s, Vaughan, Nancy Brown, M.D., and their colleagues at Vanderbilt helped identify the critical relationship between the blood-pressure regulating and clot-dissolving systems.

"Tug-of-war" between clotting and thinning the blood
Diabetes and obesity pull the dial to the left (toward clotting) by making platelets "stickier" and more sensitive to clot-forming thrombin, and by increasing production of PAl-1, which inhibits t-PA and thus clot-dissolving plasmin.  Similarly, too much fat in the blood can increase fatty acid oxidation, which in turn, accentuates the platelet-clumping actions of thromboxane over the blood-thinning actions of prostacyclin.
Illustration by Dominic Doyle
Key players in blood pressure regulation include the angiotensin converting enzyme (ACE) and the hormone aldosterone.

ACE converts angiotensin I into a small protein called angiotensin II, which causes vasoconstriction (narrowing of the blood vessels) and raises PAI-1 levels. Aldosterone, which regulates blood volume, also increases PAI-1 production.

Drugs that block the ACE enzyme, called ACE inhibitors, are widely used to lower blood pressure. By squelching excess production of PAI-1, they also can reduce the risk of a clot-induced heart attack. So can a class of diuretics that block the hormone aldosterone.

In 2002, Vaughan and his colleagues led by then post-doctoral fellow Mesut Eren (now a research assistant professor in Medicine) engineered a strain of mice that overexpresses a long-lasting form of human PAI-1.

As they age, about half the mice spontaneously form clots in their coronary arteries, without evidence of hypertension, atherosclerosis, or high lipid levels. This is evidence, Vaughan says, that high PAI-1 levels, in themselves, can precipitate clotting and a resulting heart attack.

The Vanderbilt researchers are continuing their work to determine what factors increase PAI-1 levels both in animals and in patients.

Page < 1 2 3 4 5 6 7 8 > All

View Related Articles:
How to tell if you’re at risk
The importance of knowing your numbers