Thrombospondin-4 expression is rapidly upregulated by cardiac overload.
The precise mechanisms regulating gene expression of thrombospondins (TSPs) in the heart remain incompletely understood. Here we characterized cardiac TSP-4 expression in response to pressure overload and myocardial infarction in vivo. Arginine(8)-vasopressin (AVP) infusion increased left ventricular (LV) TSP-4 mRNA levels within 30 min. Also angiotensin II infusion rapidly activated LV TSP-4 expression, TSP-4 mRNA levels being highest at 6h and protein at 72 h and 2 weeks. During remodeling process following myocardial infarction, LV TSP-4 mRNA levels increased at day one, as studied by quantitative RT-PCR. TSP-4 immunostaining was localized to endothelial cells in hypertrophied hearts of spontaneously hypertensive rats. AVP-infusion increased LV TSP-1 mRNA levels similarly to TSP-4 within 30 min showing that rapid induction of gene expression, well before the development of cardiac hypertrophy, is typical for the thrombospondin family. These results further suggest that TSP-4 may be an endothelial specific marker of cardiac overload.
Department of Pharmacology and Toxicology, Institute of Biomedicine, P.O. Box 5000, Biocenter Oulu, University of Oulu, Oulu, FIN-90014, Finland.
Erja
E
Mustonen
Jani
J
Aro
Jutta
J
Puhakka
Mika
M
Ilves
Ylermi
Y
Soini
Hanna
H
Leskinen
Heikki
H
Ruskoaho
Jaana
J
Rysä
D000375:Aging; D000818:Animals; D015415:Biomarkers; D006321:Heart; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics*; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism; D019699:Thrombospondins / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation; D020257:Ventricular Remodeling / Q000235:genetics*
D015415:Biomarkers; D019700:Thrombospondin 1; D019699:Thrombospondins; C101864:thrombospondin 4