Zhiqing Li, China
Peking University Health Science Center Department of Physiology and PathophysiologyPresenter of 1 Presentation
Microcalcification: A Pathological Characteristic and Mediator of Abdominal Aortic Aneurysm Formation
Abstract
Background and Aims
Abdominal aortic aneurysms (AAAs) are highly lethal diseases without effective clinical predictors and therapeutic targets. Vascular microcalcification as detected by fluorine-18-sodium fluoride (18F-NaF) has recently been recognized as a valuable indicator in predicting of atherosclerotic plaque rupture and AAA expansion. However, whether vascular microcalcification is involved in the pathogenesis of AAA remains elusive.
Methods
Microcalcification was analyzed in human aneurysmal aortas histologically and in angiotensin II (AngII)-infused ApoE-/- mouse aortas by 18F-NaF PET-CT scanning in chronological order in live animals.
Results
AAA patients' aortic tissue showed markedly enhanced microcalcification in the aortic media within the area proximal to elastic fiber degradation, compared to non-AAA patients. Enhanced 18F-NaF uptake preceded significant aortic expansion in mice. Microcalcification-positive mice on day 7 of AngII infusion showed dramatic aortic expansion on subsequent days 14 to 28, whereas microcalcification-negative AngII-infused mice and saline-induced mice did not develop AAA. The application of hydroxyapatite, the main component of microcalcification, aggravated AngII-induced AAA formation in vivo.RNA-sequencing analysis of the suprarenal aortas of 4-day-AngII-infused ApoE-/- mice and bioinformatics analysis with ChIP-Atlas database identified the potential involvement of the osteogenic transcriptional factor Runx2 in AAA. Consistently, VSMC-specific Runx2-deficiency markedly repressed AngII–induced AAA formation in the ApoE-/- mice compared to the control littermates.
Conclusions
Our studies have revealed microcalcification as a novel pathological characteristic and potential mediator of AAA, and targeting microcalcification may represent a promising strategy for AAA prevention and treatment.