title: Transcriptional and post-transcriptional regulation of CCN genes in failing heart.
abstract: BACKGROUND
  CCN family of proteins has been implicated in various processes in cardiovascular physiology and pathology, including angiogenesis, regeneration and fibrosis. In this study we assessed long term changes of CCN1 and CCN2 gene products abundance in the failing ventricular myocardium.
  
  
  METHODS
  Male, 12-14-weeks-old C57BL6/J and C57BL6/J (IL-6-/-) mice were used. To assess short term changes, a transient reversible ischemia model was utilized. Heart failure was caused by ligation of anterior descending coronary artery. The presence of systolic dysfunction was confirmed by echocardiography and left ventricular ANP RNA expression. Molecular analysis was performed on left ventricular samples from animals sacrificed 12-14 weeks after infarction. Western blotting and QT-PCR were used to investigate abundance of CCN proteins and RNAs, respectively.
  
  
  RESULTS
  Short ischemia resulted in marked increase of CCN1 transcript. However, three months after myocardial infarction (MI), remote myocardium showed a markedly increased expression of CCN1 protein, but not RNA. In the case of CCN2, the RNA was distinctly up-regulated, whereas the protein presented only modest, non-significant increase in failing myocardium. Expression of CCN2 RNA closely correlated with expression of ANP. Long-term telmisartan administration after infarction decreased the expression of CCN1 protein. Interleukin 6 (IL-6) deficiency caused increased CCN2 protein abundance in control animals, but the difference was absent after MI. Infarction did not increase CCN1 protein in the hearts of IL-6 deficient mice.
  
  
  CONCLUSIONS
  CCN genes are activated in heart failure. Their regulation is multidimensional both transcriptional and posttranscriptional. The involved pathways include angiotensin II and IL-6.
authors.affiliation: Department of General and Experimental Pathology, Medical University of Białystok, Białystok, Poland.
authors.forename: Tomasz A
authors.initials: TA
authors.lastname: Bonda
authors.affiliation: Department of Invasive Cardiology, Medical University of Białystok, Białystok, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kożuch
authors.affiliation: Department of General and Experimental Pathology, Medical University of Białystok, Białystok, Poland; Department of Medical Therapy, Grodno State University, Grodno, Belarus.
authors.forename: Sergei
authors.initials: S
authors.lastname: Litvinovich
authors.affiliation: Department of General and Experimental Pathology, Medical University of Białystok, Białystok, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Bialuk
authors.affiliation: Department of General and Experimental Pathology, Medical University of Białystok, Białystok, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Taranta
authors.affiliation: Chair and Department of Cardiology, Medical University of Łodz, Łódź, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Lipiec
authors.affiliation: Chair and Department of Cardiology, Medical University of Łodz, Łódź, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Szymczyk
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Białystok, Poland.
authors.forename: Włodzimierz J
authors.initials: WJ
authors.lastname: Musiał
authors.affiliation: Department of General and Experimental Pathology, Medical University of Białystok, Białystok, Poland.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Winnicka
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Białystok, Poland. Electronic address: fizklin@mp.pl.
authors.forename: Karol A
authors.initials: KA
authors.lastname: Kamiński
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D055515:Cysteine-Rich Protein 61 / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D000077333:Telmisartan; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D055515:Cysteine-Rich Protein 61; D015850:Interleukin-6; C577686:interleukin-6, mouse; D055513:Connective Tissue Growth Factor; D009320:Atrial Natriuretic Factor; D000077333:Telmisartan
keywords: CCN1; CCN2; Heart failure; IL-6; Myocardial infarction