Parallel up-regulation of FGF-2 and hyaluronan during development of cardiac hypertrophy in rat.
The importance of glycosaminoglycan hyaluronan (HA) and its receptor CD44 in cell proliferation is becoming increasingly evident. Expression of the genes coding for hyaluronan synthase 1 (HAS1), HAS2, HAS3, CD44, fibroblast growth factor-2 (FGF-2), and FGF receptor-1 (FGFR-1) and the histological evidence for increases of HA and CD44 were investigated in an experimental rat model of cardiac hypertrophy. The abdominal aorta was ligated to induce cardiac hypertrophy, and mRNAs prepared from heart tissue were analyzed after 1, 6, and 42 days. The total concentration of HA was quantified, and HA and CD44 were studied histochemically. The expression of HAS1, HAS2, CD44, and FGF-2 was considerably up-regulated at days 1 and 6 and returned to basal levels after 42 days. FGFR-1 was up-regulated at day 1 but at basal levels once more at days 6 and 42. The concentration of HA significantly increased in aorta-ligated rats. Histochemical analysis showed increased expression of CD44 in hypertrophied myocardium mainly in and around the coronary arteries. These results agree well with other studies of tissue growth (malignancies and wound healing). The increase of HA, its synthases, and receptor in parallel with FGF-2 and its receptor illustrates their complicated interplay in the development of cardiac hypertrophy. The up-regulation of both HAS1 and HAS2 indicates the importance of HA production in the hypertrophic process and the possibility that HA is needed for two different purposes for the heart to be able to adapt to the increased afterload caused by aortic ligature.
Hellman
Urban
U
Department of Public Health and Clinical Medicine/Medicine, Umeå University, Umeå, Sweden. urban.hellman@medbio.umu.se
Hellström
Martin
M
Mörner
Stellan
S
Engström-Laurent
Anna
A
Aberg
Anna-Maja
AM
Oliviero
Patricia
P
Samuel
Jane-Lise
JL
Waldenström
Anders
A
D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism*; D003238:Connective Tissue / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D050991:GATA4 Transcription Factor / Q000235:genetics; D015870:Gene Expression; D014453:Glucuronosyltransferase / Q000235:genetics; D006651:Histocytochemistry; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000032:analysis / Q000378:metabolism*; D008026:Ligation; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D050991:GATA4 Transcription Factor; C084365:Gata4 protein, rat; D018960:Hyaluronan Receptors; D016222:Fibroblast Growth Factor 2; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C491097:Has2 protein, rat; C491355:Has3 protein, rat; D000076002:Hyaluronan Synthases; C496350:Fgfr1 protein, rat; D051496:Receptor, Fibroblast Growth Factor, Type 1; D018995:Myosin Heavy Chains