Bonda Tomasz A, Kożuch Marcin, Litvinovich Sergei, Bialuk Izabela, Taranta Andrzej, Lipiec Piotr, Szymczyk Ewa, Musiał Włodzimierz J, Winnicka Maria M, Kamiński Karol A
Department of General and Experimental Pathology, Medical University of Białystok, Białystok, Poland.
Department of Invasive Cardiology, Medical University of Białystok, Białystok, Poland.
Pharmacol Rep. 2015 Apr;67(2):204-8. doi: 10.1016/j.pharep.2014.08.019. Epub 2014 Sep 3.
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.
CCN蛋白家族参与了心血管生理和病理过程的多个方面，包括血管生成、再生和纤维化。在本研究中，我们评估了衰竭心室心肌中CCN1和CCN2基因产物丰度的长期变化。
使用12 - 14周龄的雄性C57BL6/J和C57BL6/J（IL - 6 - / -）小鼠。为了评估短期变化，采用了短暂可逆性缺血模型。通过结扎冠状动脉前降支导致心力衰竭。通过超声心动图和左心室ANP RNA表达证实存在收缩功能障碍。对梗死后12 - 14周处死的动物的左心室样本进行分子分析。分别使用蛋白质印迹法和定量聚合酶链反应（QT - PCR）研究CCN蛋白和RNA的丰度。
短暂缺血导致CCN1转录物显著增加。然而，心肌梗死（MI）三个月后，远隔心肌中CCN1蛋白表达显著增加，但RNA未增加。对于CCN2，RNA明显上调，而在衰竭心肌中蛋白仅呈现适度的、无统计学意义的增加。CCN2 RNA的表达与ANP的表达密切相关。梗死后长期给予替米沙坦可降低CCN1蛋白的表达。白细胞介素6（IL - 6）缺乏导致对照动物中CCN2蛋白丰度增加，但MI后差异消失。MI并未增加IL - 6缺乏小鼠心脏中的CCN1蛋白。
CCN基因在心力衰竭中被激活。它们的调控在转录和转录后水平都是多维度的。涉及的途径包括血管紧张素II和IL - 6。
