LRP1 protects against excessive superior mesenteric artery remodeling by modulating angiotensin II-mediated signaling.

Vascular smooth muscle cells (vSMCs) exert a critical role in sensing and maintaining vascular integrity. These cells abundantly express the low-density lipoprotein receptor-related protein 1 (LRP1), a large endocytic signaling receptor that recognizes numerous ligands, including apolipoprotein E-rich lipoproteins, proteases, and protease-inhibitor complexes. We observed the spontaneous formation of aneurysms in the superior mesenteric artery (SMA) of both male and female mice in which LRP1 was genetically deleted in vSMCs (smLRP1-/- mice). Quantitative proteomics revealed elevated abundance of several proteins in smLRP1-/- mice that are known to be induced by angiotensin II-mediated (AngII-mediated) signaling, suggesting that this pathway was dysregulated. Administration of losartan, an AngII type I receptor antagonist, or an angiotensinogen antisense oligonucleotide to reduce plasma angiotensinogen concentrations restored the normal SMA phenotype in smLRP1-/- mice and prevented aneurysm formation. Additionally, using a vascular injury model, we noted excessive vascular remodeling and neointima formation in smLRP1-/- mice that was restored by losartan administration. Together, these findings reveal that LRP1 regulates vascular integrity and remodeling of the SMA by attenuating excessive AngII-mediated signaling.

Endovascular Vertebral Artery Transposition Using Flow Reversal Technique for Left Subclavian Artery Stump Syndrome.

BACKGROUND: Cerebellar strokes are a rare complication related to thoracic endovascular aortic repair (TEVAR). This can manifest in an indolent manner or as a neurological catastrophe. Often it is unclear when a surgical intervention would be needed. Patients at risk for this relatively rare complication are not easily identified. CASE: We describe an endovascular option with flow reversal for left vertebral artery transposition using stent grafts for relocating arterial inflow and excluding a floating thrombus at the proximal subclavian artery (SCA) related to a previous TEVAR. CONCLUSIONS: Ligation of the subclavian artery proximal to the vertebral artery should be considered when performing a carotid subclavian bypass for elective TEVAR. This case details a unique, less invasive approach for vertebral artery transposition and thrombus exclusion in a high-risk patient with previous neck dissection.