Biochemical Correlates of Cardiac Hypertrophy

Abstract

The incorporation of [2, 3- 3 H]proline into collagen hydroxyproline and into noncollagenous protein was measured during development of cardiac hypertrophy produced by surgical constriction of the ascending aorta in rats. Heart weight increased sharply during the first 4 days after aortic banding and then slowly rose to a plateau. Free intracellular proline concentration remained unaltered 2 days after banding and increased by 38% on the fifth postoperative day. Specific radioactivity of free proline 3 hours after injection of [ 3 H]proline was elevated by 40% on the second postoperative day but was unchanged on the fifth day. Incorporation of [ 3 H]proline into collagen hydroxyproline peaked sharply on the second day after aortic constriction (550% above control) in one experiment, and on the fourth day (330% above control) in another. The peak labeling of noncollagenous protein by [ 3 H]proline (100% over control) was less than that of collagen. To further evaluate the differences in synthetic response of muscle cells and interstitial cells to increased work load, incorporation of radioactive precursors into myosin, collagen, nuclear DNA, and noncollagenous protein were measured simultaneously, after aortic constriction. Collagen labeling was maximal either on day 2 or 4, depending on the degree of hypertrophy. Labeling of myosin and noncollagenous protein reached a plateau on day 4. Incorporation of [ 3 H]thymidine into nuclear DNA peaked on day 7. Thus both muscle cells and connective tissue cells respond independently during cardiac hypertrophy with an increased synthesis of specific proteins.