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Transcriptional and post-transcriptional regulation of CCN genes in failing heart.

Pharmacological reports : PR (2015-02-26)
Tomasz A Bonda, Marcin Kożuch, Sergei Litvinovich, Izabela Bialuk, Andrzej Taranta, Piotr Lipiec, Ewa Szymczyk, Włodzimierz J Musiał, Maria M Winnicka, Karol A Kamiński
ABSTRACT

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. 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. 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. CCN genes are activated in heart failure. Their regulation is multidimensional both transcriptional and posttranscriptional. The involved pathways include angiotensin II and IL-6.

MATERIALS
Product Number
Brand
Product Description

Telmisartan, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Telmisartan, ≥98% (HPLC), solid
USP
Telmisartan, United States Pharmacopeia (USP) Reference Standard
Telmisartan for peak identification, European Pharmacopoeia (EP) Reference Standard
Telmisartan for system suitability, European Pharmacopoeia (EP) Reference Standard