Induction of increased collagen and elastin biosynthesis in copper-deficient pig aorta

Young pigs raised on a copper-deficient diet develop severe abnormalities of connective tissue due to defective cross-linking of collagen and elastin. They eventually succumb to anemia and cardiovascular damage, the latter apparently due to the defective connective tissue metabolism. We evaluated the effects of nutritional copper deficiency upon collagen and elastin synthesis using short-term explant cultures of the medial portion of four successive segments of the descending aorta from 110-day-old pigs raised on a copper-deficient diet. Collagen synthesis was evaluated by collagenase susceptibility, and elastin synthesis was quantified by immunoprecipitation with an antiporcine-elastin antiserum. In the normal developing aorta, elastin synthesis was maximal in the upper thoracic aorta, while levels of collagen synthesis were highest in the lower abdominal aorta. Both activities subsided by 110 days postpartum. Compared with controls, the copper-deficient group showed: 1) histopathologic changes confined to the luminal half of the thoracic aorta; 2) a 1.3- to 1.6-fold increase in cellularity along the entire length of the organ; 3) a 1.3- to 2.4-fold increase in relative collagen synthesis, the greatest change occurring in the thoracic portion; 4) a 3- to 4-fold increase of relative elastin synthesis in the thoracic aorta, the abdominal aorta remaining unchanged; 5) 4- to 10-fold increases in collagen production; and 6) a greater than 15-fold increase in elastin production by the tissue of the thoracic aorta.(ABSTRACT TRUNCATED AT 250 WORDS)