AGE-DEPENDENT EXPRESSION OF FIBROSIS-RELATED GENES AND COLLAGEN DEPOSITION IN THE RAT MYOCARDIUM

Objectives: We sought to characterize the evolution, during maturation al growth and early ageing, of the messenger abundance of four genes i nvolved in cardiac fibrosis regulation (procollagens alpha(2)(I) and a lpha(1)(III), transforming growth factors beta(1) and beta(3)) and cor roborate it with the alterations in collagen deposition in cardiac int erstitium and around coronary arteries. Methods: Messenger RNA was qua ntified in LV and RV of 2-, 6-, 12- and 19-month-old male Sprague-Dawl ey rats (n = 5 per group) with Northern blot analysis. Collagen deposi tion was quantified with a semi-automated image analyser on Sirius red -stained sections of LV tissue. Results: There was an age-related mono tonous decrease of procollagen type I (COL-I) transcript abundance in LV (p < 0.001) but not in RV. Procollagen type III (COL-III) expressio n decreased rapidly during maturational growth, both in LV and RV. On the other hand, collagen deposition in myocardial interstitium and aro und coronary arteries was slightly augmented during the maturational p eriod of life (2-12 months), but with a higher rate during early agein g (up to 19 months). This was not accompanied by a significant thicken ing of the wall of coronary arteries. Transforming growth factor beta( 1)(TGF-beta(1)) and transforming growth factor beta(3)(TGF-beta(3)) tr anscript abundance showed no major variations during ageing. Conclusio ns: These results reflect a striking ventricular difference regarding the age-dependent expression of COL-I. The expression of TGF-beta(s), pleiotropic factors known to influence collagen pathway at different l evels, does not seem to be profoundly altered during ageing. The discr epancy between protein and COL-I and COL-III mRNA levels indicates dif ferences in age-related mRNA stability and/or regulation of collagen t ranslation. (C) 1998 Elsevier Science ireland Ltd. All rights reserved .