Perivascular inflammation in the progression of aortic aneurysms in Marfan syndrome.
Authors
Affiliations (5)
Affiliations (5)
- Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
- Marfan Syndrome Center, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
- Department of Cardiovascular Medicine, Kanto Central Hospital of the Mutual Aid Association of Public School Teachers, Tokyo, Japan.
- Department of Cardiac & Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
- nternational University of Health and Welfare, Tokyo, Japan.
Abstract
Inflammation plays important roles in the pathogenesis of vascular diseases. We here show the involvement of perivascular inflammation in aortic dilatation of Marfan syndrome (MFS). In the aorta of MFS patients and Fbn1C1041G/+ mice, macrophages markedly accumulated in periaortic tissues with increased inflammatory cytokine expression. Metabolic inflammatory stress induced by a high-fat diet (HFD) enhanced vascular inflammation predominantly in periaortic tissues and accelerated aortic dilatation in Fbn1C1041G/+ mice, both of which were inhibited by low-dose pitavastatin. HFD feeding also intensifies structural disorganization of the tunica media in Fbn1C1041G/+ mice, including elastic fiber fragmentation, fibrosis, and proteoglycan accumulation, along with increased activation of TGF-β downstream targets. Pitavastatin treatment mitigated these alterations. For non-invasive assessment of PVAT inflammation in a clinical setting, we developed an automated analysis program for CT images using machine learning techniques to calculate the perivascular fat attenuation index of the ascending aorta (AA-FAI), correlating with periaortic fat inflammation. The AA-FAI was significantly higher in patients with MFS compared to patients without hereditary connective tissue disorders. These results suggest that perivascular inflammation contributes to aneurysm formation in MFS and might be a potential target for preventing and treating vascular events in MFS.