Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice

Abstract

Myeloid cells are crucial for the development of vascular inflammation. Low-density lipoprotein receptor-related protein 8 (LRP8) or Apolipoprotein E receptor 2 (ApoER2), is expressed by macrophages, endothelial cells and platelets and has been implicated in the development of cardiovascular diseases. Our aim was to evaluate the role of LRP8, in particular from immune cells, in the development of vascular inflammation. Methods. LRP8+/+ and LRP8−/− mice (on B6;129S background) were infused with angiotensin II (AngII, 1 mg/kg/day for 7 to 28 day) using osmotic minipumps. Blood pressure was recorded using tail cuff measurements. Vascular reactivity was assessed in isolated aortic segments. Leukocyte activation and infiltration were assessed by flow cytometry of aortic tissue and intravital videomicroscopy imaging. Histological analysis of aortic sections was conducted using sirius red staining. Results. AngII infusion worsened endothelial-dependent vascular relaxation and immune cells rolling and adherence to the carotid artery in both LRP8+/+ as well as LRP8−/− mice. However, only LRP8−/− mice demonstrated a drastically increased mortality rate in response to AngII due to aortic dissection. Bone marrow transplantation revealed that chimeras with LRP8 deficient myeloid cells phenocopied LRP8−/− mice. Conclusion. AngII-infused LRP8 deficient mice could be a useful animal model to study aortic dissection reflecting the lethality of this disease in humans.

Circ_0022920 Maintains the Contractile Phenotype of Human Aortic Vascular Smooth Muscle Cells Via Sponging microRNA‐650 and Promoting Transforming Growth Factor Beta Receptor 1 Expression in Angiotensin II‐Induced Models for Aortic Dissection

“…Angiotensin II contributes to the contraction of human airway smooth muscle and induces AD in mice. 29 , 30 To further study the role of circ_0022920 , HASMCs were treated with angiotensin II to establish an in vitro cell model for AD. We found that circ_0022920 was significantly downregulated in angiotensin II‐treated HASMCs (Figure 3A ).…”

The short-chain fatty acid butyrate exerts a specific effect on VE-cadherin phosphorylation and alters the integrity of aortic endothelial cells

“…Ang-II is a critical factor at the systemic and cellular level for the pathogenesis of vascular diseases in general ( Berk et al, 2000 ) and, in particular, for aortic diseases like aortic dissection and aneurysms ( Lagrange et al, 2020 ; Wu et al, 2021 ). Experimental work suggests that Ang-II in conjunction with RAGE (receptor for advanced glycation end products) increases phospho-VEC tyrosine-731 and VEC disruption that correlate with the induction of hyperpermeability of HUVECs and murine aortas ( Jeong et al, 2019 ).…”

Independent and Interactive Roles of Immunity and Metabolism in Aortic Dissection

“…Activated monocytes and platelet receptor glycoprotein Ib alpha (GPIbα) participate in local thrombin amplification through coagulation factor XI (FXI), thereby promoting the development of vascular inflammation and hypertension and accelerating the progression of AD [40]. Additionally, low-density lipoprotein receptor-related protein 8 (LRP8) is released from monocytes and can induce vascular inflammation and endothelial dysfunction, leading to AD [41].…”