Macrophage-derived human resistin promotes perivascular adipose tissue dysfunction in experimental inflammatory arthritis.

Cardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA). Resistin is an adipokine that induces adipose tissue inflammation and activation of monocytes/macrophages via adenylate cyclase-associated protein-1 (CAP1). Resistin levels are increased in RA and might cause perivascular adipose tissue (PVAT) dysfunction, leading to vascular damage and CVD. This study aimed to investigate the role of resistin in promoting PVAT dysfunction by increasing local macrophage and inflammatory cytokines content in antigen-induced arthritis (AIA). Resistin pharmacological effects were assessed by using C57Bl/6J wild-type (WT) mice, humanized resistin mice expressing human resistin in monocytes-macrophages (hRTN+/-/-), and resistin knockout mice (RTN-/-) with AIA and respective controls. We investigated AIA disease activity and functional, cellular, and molecular parameters of the PVAT. Resistin did not contribute to AIA disease activity and its concentrations were augmented in the PVAT and plasma of WT AIA and hRTN+/-/- AIA animals. In vitro exposure of murine arteries to resistin impaired vascular function by decreasing the anti-contractile effect of PVAT. WT AIA mice and hRTN+/-/- AIA mice exhibited PVAT dysfunction and knockdown of resistin prevented it. Macrophage-derived cytokines, markers of types 1 and 2 macrophages, and CAP1 expression were increased in the PVAT of resistin humanized mice with AIA, but not in knockout mice for resistin. This study reveals that macrophage-derived resistin promotes PVAT inflammation and dysfunction regardless of AIA disease activity. Resistin might represent a translational target to reduce RA-driven vascular dysfunction and CVD.

Angiotensin axis blockade, acute kidney injury, and perioperative morbidity in patients undergoing colorectal surgery: A retrospective cohort study.

Patients undergoing surgery and taking angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) are susceptible to complications related to intraoperative hypotension. Perioperative continuation of such medications in patients undergoing colorectal surgery may be associated with more harm than benefit, as these patients are often exposed to other risk factors which may contribute to intraoperative hypotension. Our objectives were to assess the incidence and severity of postinduction hypotension as well as the rates of acute kidney injury (AKI), 30-day all-cause mortality, 30-day readmission, and hospital length of stay in adult patients undergoing colorectal surgery who take ACEi/ARB.We performed a retrospective chart review of patients undergoing colorectal surgery of ≥4 hour duration at a tertiary care academic medical center between January 2011 and November 2016. The preoperative and intraoperative characteristics as well as postoperative outcomes were compared between patients taking ACEi/ARB and patients not taking these medications.Of the 1020 patients meeting inclusion criteria, 174 (17%) were taking either ACEi or ARB before surgery. Patients taking these medications were more likely to receive both postinduction and intraoperative phenylephrine and ephedrine. The incidences of postoperative AKI (P = .35), 30-day all-cause mortality (P = .36), 30-day hospital readmission (P = .45), and hospital length of stay (P = .25), were not significantly different between the 2 groups.Our results support the current recommendation that ACEi/ARB use is probably safe within the colorectal surgery population during the perioperative period. Intraoperative hypotension should be expected and treated with vasopressors.