A new procedure to induce aortic aneurysms in mice.

Aortic aneurysms (AAs) are a major public health challenge, featured by a progressive impairs in aortic wall integrity that drives to aortic dilation and, in end stage, to its rupture. Despite important advances in the surgical treatment of aortic aneurysms, there is currently no pharmacological intervention that prevents their development, reduces their expansion, or avoids their rupture. In addition to classic risk factors such age or gender, several heritable connective tissue disorders have been associated with AA developing, highlighting the role of extracellular matrix (ECM) genes alterations in the developing of AA. In this sense, we have recently demonstrated that global deletion of the cellular communicating network factor 2 (CCN2), previously known as connective tissue growth factor (CTGF) due to its role in the extracellular matrix formation, predisposes to early and lethal AAs development after Angiotensin II (Ang II) infusion in mice. Here, we detail the protocol to induce and detect AAs generation in inducible global CCN2 knockout mice after Ang II infusion which allow the characterization of CCN role in AA development and may help to the development of pharmacological target for AA treatment.

Rodrigues-Díez R ，Tejera-Muñoz A ，Rodrigues-Diez RR 《Methods in Cell Biology》

CCN2 (Cellular Communication Network Factor 2) Deletion Alters Vascular Integrity and Function Predisposing to Aneurysm Formation.

Rodrigues-Díez RR ，Tejera-Muñoz A ，Esteban V ，Steffensen LB ，Rodrigues-Díez R ，Orejudo M ，Rayego-Mateos S ，Falke LL ，Cannata-Ortiz P ，Ortiz A ，Egido J ，Mallat Z ，Briones AM ，Bajo MA ，Goldschmeding R ，Ruiz-Ortega M ... -  《-》

Endothelial cell-specific deficiency of Ang II type 1a receptors attenuates Ang II-induced ascending aortic aneurysms in LDL receptor-/- mice.

Rateri DL ，Moorleghen JJ ，Balakrishnan A ，Owens AP 3rd ，Howatt DA ，Subramanian V ，Poduri A ，Charnigo R ，Cassis LA ，Daugherty A ... -  《-》

Smooth muscle cell deletion of low-density lipoprotein receptor-related protein 1 augments angiotensin II-induced superior mesenteric arterial and ascending aortic aneurysms.

Low-density lipoprotein receptor-related protein 1 (LRP1), a multifunctional protein involved in endocytosis and cell signaling pathways, leads to several vascular pathologies when deleted in vascular smooth muscle cells (SMCs). The purpose of this study was to determine whether LRP1 deletion in SMCs influenced angiotensin II-induced arterial pathologies. LRP1 protein abundance was equivalent in selected arterial regions, but SMC-specific LRP1 depletion had no effect on abdominal and ascending aortic diameters in young mice. To determine the effects of LRP1 deficiency on angiotensin II vascular responses, SMC-specific LRP1 (smLRP1(+/+)) and smLRP1-deficient (smLRP1(-/-)) mice were infused with saline, angiotensin II, or norepinephrine. Several smLRP(-/-) mice died of superior mesenteric arterial (SMA) rupture during angiotensin II infusion. In surviving mice, angiotensin II profoundly augmented SMA dilation in smLRP1(-/-) mice. SMA dilation was blood pressure dependent as demonstrated by a similar response during norepinephrine infusion. SMA dilation was also associated with profound macrophage accumulation, but minimal elastin fragmentation. Angiotensin II infusion led to no significant differences in abdominal aorta diameters between smLRP1(+/+) and smLRP1(-/-) mice. In contrast, ascending aortic dilation was exacerbated markedly in angiotensin II-infused smLRP1(-/-) mice, but norepinephrine had no significant effect on either aortic region. Ascending aortas of smLRP1(-/-) mice infused with angiotensin II had minimal macrophage accumulation but significantly increased elastin fragmentation and mRNA abundance of several LRP1 ligands including MMP-2 (matrix metalloproteinase-2) and uPA (urokinase plasminogen activator). smLRP1 deficiency had no effect on angiotensin II-induced abdominal aortic aneurysm formation. Conversely, angiotensin II infusion in smLRP1(-/-) mice exacerbated SMA and ascending aorta dilation. Dilation in these 2 regions had differential association with blood pressure and divergent pathological characteristics.

Davis FM ，Rateri DL ，Balakrishnan A ，Howatt DA ，Strickland DK ，Muratoglu SC ，Haggerty CM ，Fornwalt BK ，Cassis LA ，Daugherty A ... -  《-》

Vascular Smooth Muscle Cell Plasticity and Autophagy in Dissecting Aortic Aneurysms.

Clément M ，Chappell J ，Raffort J ，Lareyre F ，Vandestienne M ，Taylor AL ，Finigan A ，Harrison J ，Bennett MR ，Bruneval P ，Taleb S ，Jørgensen HF ，Mallat Z ... -  《-》