Apolipoprotein A-I Mimetic Peptide Reverses Aortic Valve Stenosis

Cardiovascular disease researchers have used a peptide mimetic of apolipoprotein A-I (apo A-I), the main protein component of the good cholesterol carrier HDL (high density lipoprotein), to reverse the effects of aortic valve stenosis (AVS).

AVS is the most common form of heart valve disease in Western countries. The disease is characterized by a narrowing of the aortic valve opening, causing a difference in blood pressure between the heart and the rest of the body, which is particularly dangerous for the patient.

Earlier studies had indicated that increased serum levels of apo A-I had a positive effect on AVS. However, inducing an increase in either apo A-I or HDL has proven to be a difficult task. To avoid problems with administering large molecules, investigators at the Montreal Heart Institute Research Center (Canada) created an apo A-I mimetic peptide with the same active potential as the much larger apo A-I.

In the study, 15 New Zealand White male rabbits received a cholesterol-enriched diet and vitamin D2 until significant AVS was detected by echocardiography. The enriched diet was then stopped to mimic cholesterol-lowering therapy and animals were allocated randomly to receive saline or an ApoA-I mimetic peptide three times per week for 2 weeks

Results published in the April 14, 2008, on-line edition of the British Journal of Pharmacology revealed that aortic valve area increased significantly by 25% in the treated group after 14 days of treatment. Likewise, aortic valve thickness decreased by 21% in the treated group, whereas it was unchanged in controls.

"We are delighted to see that the new type of drug used, based on HDL, led to the regression of the aortic valve stenosis in an experimental model,” said senior author Dr. Jean-Claude Tardif, professor of medicine at the Montreal Heart Institute Research Center. "This important discovery warrants further clinical studies on patients suffering from this frequent disease. This new medical option could possibly provide us with an alternative to the cardiac surgery of aortic valve replacement.”


Related Links:
Montreal Heart Institute Research Centre