Increased Activity of Lysosomal Enzymes in Experimental Atherosclerosis, and the Effect of Cortisone

Abstract

The activity of beta-glucuronidase is increased in atherosclerotic human arteries (1)(2)(3) . Noting that beta-glucuronidase is a key marker enzyme in evaluating lysosomal enzyme activity, we decided to investigate other lysosomal enzymes in human atherosclerotic vessels. I t was found that in addition to beta-glucuronidase, the lysosomal enzymes, acid phosphatase, cathepsin and aryl sulfatase showed increased activity in human atherosclerotic aortas (4). The present report describes the activities of these four enzymes in the aortas of rabbits in which atherosclerosis has been induced by adding cholesterol to the diet.The effect of cortisone added to the diet has been observed. Cortisone tends to increase the level of serum cholesterol in the cholesterol-fed animals; nevertheless, this compound greatly decreases the intensity of atherosclerosis (5, 6 ) . I t is of interest that cortisone exerts a strong effect on lysosomal membranes (7). We have therefore investigated the effect of cortisone on the activity of the lysosomal enzymes in the cholesterol-fed rabbits.Materials and Methods. Male, white New Zealand rabbits, weighing 2.0 to 2.5 kg were fed the diets ad libitum for a period of 100 days. The control group of 5 rabbits received standard rabbit chow. Another 10 animals were fed the same chow to which was added 1 c/r cholesterol acetate. Of these, five survived the 100-day. period. A third group of 8 rabbits received the cholesterol-containing diet to which was added cortisone acetate to give a concentration of 0.005%]. Of the third group, 5 rabbits were alive a t the end of the experiment. The animals were sacrificed instantly by mechanical means a t 100 days. *Aided by a grant from The William H. Donner Foundation.The aortas were dissected out and scored grossly with a hand lens for atherosclerotic involvenient by two observers working independently. The arch, the thoracic and abdominal portions of the aorta were graded separately on a scale of 1 to 4, and the total score was recorded: 1+ represents fatty streaks and small plaques covering up to 10% of the area; 2+ indicates 10-25%; 3+, 25-50%; 4+ from 50% to total involvement.Representative samples of each portion of the aorta were taken for histologic examination, and the remainder were employed for the enzyme assays. The histological examinations were performed by Dr. M. A. Farooki, Professor of Pathology, Khyber Medical College, Peshawar University, who a t the time of these experiments was Visiting Pathologist at the Philadelphia General Hospital.For the determination of enzyme activities, the aortas were carefully stripped of adventitia. The intima-media residuals were then homogenized by hand in a cold 0.25 M sucrose solution with a glass tissue grinder. The homogenate was centrifuged a t 2520g for 10 min to remove debris. The supernatant was employed for the estimation of the enzyme activities. The enzymic tests were all carried out a t 37". Activities are expressed in units//gram of tissue; 1 unit refers to the decomposition of 1 pg or 1 pmole of ...

Modification of the Effects of Hypertension on Lysosomes and Connective Tissue in the Rat Aorta

“…Somewhat analogous to the findings in this paper are those by Curreri et al (38), who showed that lysosomal enzymes are markedly increased in atherosclerotic plaque-laden aortic tissue of rabbits fed an atherogenic diet. Administration of cortisone in addition to the diet aggravated the hypercholesterolemia of these rabbits but resulted in complete protection from disease and maintenance of activities of lysosomal enzymes at normal levels.…”

Lysosomal Enzymes in Aortas of Species Susceptible and Resistant to Atherosclerosis

“…This is true for human and rabbit as shown in our laboratory (1,2 ) . It seems reasonable to expect that a scavenging system such as the lysosoimes would be ac- a Activities released from the 17000g lysosome-like fraction were measured.…”

“…Curreri et d . ( 2 ) studied lysosomal enzymes in aortas of rabbits with cholesterol-induced atherosclerosis. There was a marked increase in activity of the lysosomal enzymes in the atherosclerotic aortas.…”

Proteases in cardiometabolic diseases: Pathophysiology, molecular mechanisms and clinical applications

“…Early studies documented that increased cathepsin activity was associated with experimental atherosclerosis [188]. Two decades ago, Reddy and the colleague observed that human macrophages secrete the active form of cathepsin S, B and L [189].…”