Adventitial recruitment of Lyve-1- macrophages drives aortic aneurysm in an angiotensin-2-based murine model.

OBJECTIVE: Aortic macrophage accumulation is characteristic of the pathogenesis of abdominal aortic aneurysm (AAA) but the mechanisms of macrophage accumulation and their phenotype are poorly understood. Lymphatic vessel endothelial receptor-1 (Lyve-1+) resident aortic macrophages independently self-renew and are functionally distinct from monocyte-derived macrophages recruited during inflammation. We hypothesized that Lyve-1+ and Lyve-1- macrophages differentially contribute to aortic aneurysm. Approach and results: Angiotensin-2 and ß-aminopropionitrile (AT2/BAPN) were administered to induce AAA in C57BL/6J mice. Using immunohistochemistry (IHC), we demonstrated primarily adventitial accumulation of aortic macrophages, and in association with areas of elastin fragmentation and aortic dissection. Compared with controls, AAA was associated with a relative percent depletion of Lyve-1+ resident aortic macrophages and accumulation of Lyve-1- macrophages. Using CD45.1/CD45.2 parabiosis, we demonstrated aortic macrophage recruitment in AAA. Depletion of aortic macrophages in CCR2-/- mice was associated with reduced aortic dilatation indicating the functional role of recruitment from the bone marrow. Depletion of aortic macrophages using anti-macrophage colony-stimulating factor 1 receptor (MCSF1R)-neutralizing antibody (Ab) reduced the incidence of AAA. Conditional depletion of Lyve-1+ aortic macrophages was achieved by generating Lyve-1wt/cre Csf1rfl/fl mice. Selective depletion of Lyve-1+ aortic macrophages had no protective effects following AT2/BAPN administration and resulted in increased aortic dilatation in the suprarenal aorta. CONCLUSIONS: Aortic macrophage accumulation in AAA derives from adventitial recruitment of Lyve-1- macrophages, with relative percent depletion of Lyve-1+ macrophages. Selective targeting of macrophage subtypes represents a potential novel therapeutic avenue for the medical treatment of AAA.

Type IA endoleak caused by interlocked suprarenal bare-metal stents after endovascular abdominal aortic aneurysm repair with successful endovascular rescue.

A physically active 90-year-old man underwent endovascular repair of an asymptomatic but enlarging abdominal aortic aneurysm. Postoperative computed tomography demonstrated entanglement of nonadjacent proximal bare-metal stents. This was associated with graft infolding and a type IA endoleak. The patient underwent percutaneous transluminal angioplasty and placement of a Palmaz stent. Subsequent surveillance imaging showed resolution of the type I endoleak >1 year later. This report demonstrates an uncommon cause of stent graft infolding, an already rare complication of endovascular aneurysm repair, and highlights the need to carefully assess the morphologic appearance of the proximal fixation stents after graft deployment.

Interleukin-3 is required for thoracic aneurysm and dissection in a mouse model.

The pathogenesis of thoracic aortic aneurysm and dissection (TAAD) is complex and incompletely understood. The hallmarks of the disease process are aortic inflammatory cell infiltration and protease mediated elastic fiber disruption. In a study recently published in Clinical Science (2018) 132 (6), 655-668), Liu et al explore the mechanism through which aortic vascular smooth cells and macrophages participate in TAAD using a mouse model. The authors propose that interleukin-3 (IL-3) released from aortic vascular smooth cells is central to the disease process. IL-3 stimulated matrix metalloproteinase 12 (MMP12) release from macrophages via mitogen activated protein kinase pathways. MMP12 is a protease known to be involved in both aortic aneurysm and dissection. IL-3 knockout mice had significantly reduced aortic wall MMP12, and reduced protease activity. This was associated with protection against TAAD.

The effect of obesity on acute kidney injury after cardiac surgery.

OBJECTIVE: Postoperative acute kidney injury is a frequent and serious consequence of cardiac surgery. We undertook to investigate the association of obesity and the risk of acute kidney injury development after cardiac surgery. METHODS: A total of 432 patients who underwent cardiac surgery with cardiopulmonary bypass between October 2009 and August 2010 were included in the final retrospective analysis. Obesity was defined as body mass index 30 kg/m(2) or greater. Acute kidney injury was defined as a creatinine increase of 25% or more from baseline at 48 hours after surgery. RESULTS: The overall incidence of acute kidney injury was 29.9% (n = 129). There was an increased incidence of postoperative renal impairment in the obese versus nonobese cohort; however, this was not statistically significant (39% vs 25.9%, P = .007). Multivariate logistic regression revealed that body mass index 30 kg/m(2) or greater was independently associated with the development of postoperative acute kidney injury (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.27-3.54; P = .004), as were age (OR, 0.98; 95% CI, 0.96-1.0; P = .04) and cardiopulmonary bypass time (OR, 0.99; 95% CI, 0.98-1.0; P = .048). CONCLUSIONS: Obesity with body mass index 30 kg/m(2) or greater is independently associated with an increased risk of acute kidney injury after cardiac surgery. Further understanding of the molecular basis of this association is critical to the design of preventative strategies.