| Background:Cardiac ankyrin repeat protein(CARP),as an ankyrin-repeated protein not only acts as a nuclear transcriptional co-factor in the nucleus,but also serves as an important component of muscle sarcomere in the cytoplasm.Previous studies have demonstrated increased expression of CARP in cardiovascular diseases,however,its role in dilated cardiomyopathy is still unclear.Methods and results:Western blot analysis of CARP protein expression revealed increased CARP expression in heart tissue of dilated cardiomyopathy compared to normal heart.Next,we generated CARP transgenic mouse and CARP overexpressed AAV9 injected mouse model,and found CARP overexpression induced cardiac chamber dilation and systolic dysfunction.Overexpressed CARP was dominantly distributed in nucleus as revealed by immunostaining of CARP in heart sections.Furthermore,microarray analysis revealed altered expression of cardiac genes associated with cardiac contraction and sarcomere structure.Conclusion:CARP overexpression induces dilated cardiomyopathy possibly through regulation of cardiac genes expression.Our study defines the role and molecular pathyway of CARP in dilated cardiomyopathy,and provides new diagnostic and therapeutic avenue for cardiovascular diseases. |
