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Aims: IFN-beta (IFNβ) signalling is increased in patients with insufficient coronary collateral growth (i.e. arteriogenesis) and IFNβ hampers arteriogenesis in mice. A downside of most pro-arteriogenic agents investigated in the past has been their pro-atherosclerotic properties, rendering them unsuitable for therapeutic application. Interestingly, type I IFNs have also been identified as pro-atherosclerotic cytokines and IFNβ treatment increases plaque formation and accumulation of macrophages. We therefore hypothesized that mAb therapy to inhibit IFNβ signalling would stimulate arteriogenesis and simultaneously attenuate--rather than aggravate--atherosclerosis. Methods and results: In a murine hindlimb ischaemia model, atherosclerotic low-density lipoprotein receptor knockout (LDLR-/-) micewere treated during a 4-week period with blocking MAbs specific for mouse IFN-α/β receptor subunit 1 (IFNAR1) or murine IgG isotype as a control. The arteriogenic responsewas quantified using laser Doppler perfusion imaging (LDPI) aswell as immunohistochemistry. Effects on atherosclerosis were determined by quantification of plaque area and analysis of plaque composition. Downstream targets of IFNβ were assessed by real-time PCR(RT-PCR) in the aortic arch. Hindlimb perfusion restoration after femoral artery ligation was improved in mice treated with anti-IFNAR1 compared with controls as assessed by LDPI. Thiswas accompanied by a decrease inCXCL10expression in the IFNAR1 MAb-treated group. Anti-IFNAR1 treatment reduced plaque apoptosis without affecting total plaque area or other general plaque composition parameters. Results were confirmed in a short-term model and in apolipoprotein E knockout (APOE)-/- mice. Conclusion: Monoclonal anti-IFNAR1 therapy during a 4-week treatment period stimulates collateral artery growth in mice and did not enhance atherosclerotic burden. This is the first reported successful strategy using MAbs to stimulate arteriogenesis. [ABSTRACT FROM AUTHOR]

Aims: Complete non-culprit (NC) revascularization may help reduce recurrent events after NSTEMI, especially if NC lesions would harbor high-risk plaque features similar to STEMI. The study aimed to assess differences in fractional flow reserve (FFR)-negative NC plaque morphology in patients presenting with NSTEMI versus STEMI and assess the association of high-risk plaque morphology and clinical outcome., Methods and Results: In the prospective PECTUS-obs study, 438 patients presenting with myocardial infarction (MI) underwent optical coherence tomography (OCT) of all FFR-negative intermediate NC lesions. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE, all-cause mortality, non-fatal MI or unplanned revascularization) at two-year follow-up. Four hundred and twenty patients had at least one analyzable OCT, including 203 (48.3%) with NSTEMI and 217 (51.7%) with STEMI. The prevalence of high-risk plaques (HRP), including thin-cap fibroatheromas (TCFA), plaque rupture and thrombus, was comparable between groups. MACE occurred in 29 (14.3%) NSTEMI patients and 16 (7.4%) STEMI patients (Punivariable=0.025 and Pmultivariable=0.270). Incidence of MACE was numerically higher among patients with HRP, irrespective of the clinical presentation at index (Pinteraction=0.684). Among high-risk plaque criteria, plaque rupture was associated with MACE in both NSTEMI (p<0.001) and STEMI (p=0.020)., Conclusion: Presence of NC HRP is comparable between NSTEMI and STEMI and leads to numerically higher event rates in both. These results call for additional research on complete revascularization in NSTEMI and treatment of HRP., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)