RT Journal Article
T1 Sustained Focal Vascular Inflammation Accelerates Atherosclerosis in Remote Arteries
A1 Lavín Plaza, Begoña
A1 Phinikaridou, Alkystis
A1 Andia, Marcelo
A1 Potter, Myles
A1 Lorrio, Silvia
A1 Rashid, Imran
A1 Botnar, Rene
AB OBJECTIVE: Evidence from preclinical and clinical studies has demonstrated that myocardial infarction promotes atherosclerosis progression. The impact of focal vascular inflammation on the progression and phenotype of remote atherosclerosis remains unknown. APPROACH AND RESULTS: We used a novel ApoE−/− knockout mouse model of sustained arterial inflammation, initiated by mechanical injury in the abdominal aorta. Using serial in vivo molecular MRI and ex vivo histology and flow cytometry, we demonstrate that focal arterial inflammation triggered by aortic injury, accelerates atherosclerosis in the remote brachiocephalic artery. The brachiocephalic artery atheroma had distinct histological features including increased plaque size, plaque permeability, necrotic core to collagen ratio, infiltration of more inflammatory monocyte subsets, and reduced collagen content. We also found that arterial inflammation following focal vascular injury evoked a prolonged systemic inflammatory response manifested as a persistent increase in serum IL-6 (interleukin 6). Finally, we demonstrate that 2 therapeutic interventions—pravastatin and minocycline—had distinct anti-inflammatory effects at the plaque and systemic level. CONCLUSIONS: We show for the first time that focal arterial inflammation in response to vascular injury enhances systemic vascular inflammation, accelerates remote atheroma progression and induces plaques more inflamed, lipid-rich, and collagenpoor in the absence of ischemic myocardial injury. This inflammatory cascade is modulated by pravastatin and minocycline treatments, which have anti-inflammatory effects at both plaque and systemic levels that mitigate atheroma progression.
PB Lippincott Williams and Wilkins
SN 1524-4636
YR 2020
FD 2020
LK https://hdl.handle.net/20.500.14352/97831
UL https://hdl.handle.net/20.500.14352/97831
LA eng
NO Lavin Plaza, Begoña, et al. «Sustained Focal Vascular Inflammation Accelerates Atherosclerosis in Remote Arteries». Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 40, n.o 9, septiembre de 2020, pp. 2159-70. https://doi.org/10.1161/ATVBAHA.120.314387.
NO Engineering and Physical Sciences Research Council (Reino Unido)
NO British Heart Foundation (Reino Unido)
NO King’s BHF Centre for Research Excellence (Reino Unido)
DS Docta Complutense
RD 11 abr 2025