REGULATION OF FIBRILLAR COLLAGEN GENE-EXPRESSION AND PROTEIN ACCUMULATION IN VOLUME-OVERLOADED CARDIAC-HYPERTROPHY

Background Interstitial collagen accumulation has been extensively dem onstrated to be increased at both mRNA and protein levels in pressure- overloaded cardiac hypertrophy. However, few data are available regard ing the effects of volume overload on myocardial collagens. Methods an d Results To determine whether the alterations of collagens may occur in volume-overloaded cardiac hypertrophy, we measured collagen types I and III mRNA levels and protein accumulation in left ventricular (LV) myocardium of rats at 3, 7, and 28 days after the creation of an aort ocaval (AC) shunt. Eccentric LV hypertrophy was produced in rats with AC shunting. Northern blot analysis on RNA extracted from LV tissue in dicated that the steady state mRNA levels for both type I and III coll agen were persistently upregulated in AC shunt rats compared with sham -operated control rats. In contrast, the biochemical collagen protein concentration and morphometric collagen volume fraction were comparabl e between sham-operated control and AC shunt rats at any study time po int. Furthermore, the immunohistochemical staining of types I and III collagen and Sirius red staining on myocardial tissue sections reveale d no significant alterations in the distribution or density of fibrill ar collagens in AC shunt rats. Tissue collagenase activity was not dif ferent between control and AC shunt rats after 28 days. Conclusions Ca rdiac volume overload increases LV collagen mRNA as does pressure over load. However, in contrast to pressure-overloaded hypertrophy, the upr egulation of collagen transcriptional activity does not result in subs equent myocardial fibrosis in volume-overloaded hypertrophy due to AC shunting. Therefore, the upregulation of collagen gene expression and protein accumulation might be different in pressure-overloaded and vol ume-overloaded hypertrophy.