TY - JOUR
T1 - SUSTAINED FOCAL VASCULAR INFLAMMATION ACCELERATES ATHEROSCLEROSIS IN REMOTE ARTERIES
AU - Lavin Plaza, Begona
AU - Phinikaridou, Alkystis
AU - Andia Kohnenkampf, Marcelo
AU - Potter, Myles
AU - Lorrio, Silvia
AU - Rashid, Imran
AU - Botnar, Rene
PY - 2020
Y1 - 2020
N2 - 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 collagen-poor 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.
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 collagen-poor 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.
UR - http://www.scopus.com/inward/record.url?scp=85090080220&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.120.314387
DO - 10.1161/ATVBAHA.120.314387
M3 - Article
SN - 1079-5642
SP - 2159
EP - 2170
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
ER -