Elastase in the prevention of arterial aging and the treatment of atherosclerosis.

Arterial aging is defined as the age-related structural and functional changes in arteries from the precapillary to the aortic level. These include atheromatous changes. Such changes can be estimated in medium-sized or larger arteries by clinical diagnostic studies, including B-mode echography of the carotid artery (thickening of the intima, plaque formation and increase in luminal diameter) and abdominal aorta (plaque formation and increase in luminal diameter). Doppler echography (pulse wave velocity; PWV) and autopsy studies. These changes include distension of the lumen, increased arterial wall thickness (which may be associated with atherosclerotic plaques) and decreased extensibility of the arterial wall. Since 1981, an anti-atherosclerotic drug containing porcine pancreatic elastase 1 (PPE1) has been used for the prevention of arterial aging and the treatment of atherosclerosis in elderly patients in Japan. So far, the age-related increase in PWV has been found to be lower in those who take PPE1 than in controls. The atherosclerotic index of the carotid artery has also been found to be lower in subjects receiving PPE1 treatment than in control subjects. The pharmacological basis of PPE1 therapy, although paradoxical to the consensus opinion of the pathogenic role of elastase in western countries, is discussed with reference to data gathered in Japan. The pathomechanism of arterial aging and atherosclerosis, with special reference to elastin, is reviewed along with the presentation of some of our data.