CCN2 deletion promotes changes in the aortic protein expression pattern
To evaluate changes in aortic protein expression caused by acquired CCN2 deficiency, a panel of 17 proteins related to ECM and/or VSMCs status, including CCN2, was studied by multiple reaction monitoring mass spectrometry (MRM-MS) analysis. CCN2 protein was detected in control aorta, supporting its important role in vascular structure and functions, as a key ECM component. As observed at the gene expression level (Suppl Figure 3 ), aortic CCN2 protein level was significantly reduced in CCN2-KO mice (Suppl Table 1 ), demonstrating the efficacy of gene targeting. Alpha smooth muscle actin (ACTA2) expression was significantly decreased (around 20% reduction) and myosin heavy chain 9 was significantly increased in CCN2-KO mice, suggesting a CCN2-related regulation of both proteins (Suppl Table 1) . Interestingly, CCN2 was the most Ang II-upregulated protein in WT mice in our panel (2.36-fold increase), suggesting an important role of CCN2 in Ang II-mediated vascular responses and, therefore, in the aortic protective adaptive response induced after Ang II infusion.