Giant cell arteritis (GCA) is an inflammatory cranial and/or extracranial vasculitis. Although cranial GCA is widely recognized, extracranial GCA is underdiagnosed because of its nonspecific and atypical presentations. We report a case of asymptomatic extracranial GCA with ascending thoracic aortopathy discovered incidentally during surgical mitral valve repair. (Level of Difficulty: Intermediate.).

OBJECTIVE: To explore the thoracic ascending aortic （TAA） pathophysiological characteristics of heterozygous mutant Myh11 R247C/+ mice under the norepinephrine-induced hypertension mode.
METHODS: Female heterozygous mutant Myh11 R247C/+ and wild type Myh11 +/+ mice were selected as experimental group (HET group) and control group (WT group)，respectively. The hypertensive model was induced by intraperitoneal injection of norepinephrine (NE)，and TAA diameter and invasive blood pressure (Bp) data were collected dynamically in real time using high-frequency ultrasound imaging and invasive arterial blood pressure monitoring technique，so as to indirectly analyze TAA compliance of two groups of mice. At the same time，the incidences of hemothorax and TAA rupture were further analyzed by autopsy and histology.
RESULTS: After injection of NE，heterozygous mice did not show a higher Bp increase percentage in systole or diastole comparing with wildtype mice. However，heterozygous mice exhibited 17% and 32% higher TAA diameter dilation percentage than wildtype ones in systole and diastole respectively. Two heterozygous mice had TAA dissection and rupture，and the incidence of hemothorax in heterozygous mice (3/5) was higher than that in wildtype (0/5).
CONCLUSIONS: It was very likely that the altered TAA wall compliance of mutant Myh11 R247C/+ mice had led to a higher TAA dilation degree than that in wildtype，and even could be the potential reason of TAA dissection and rupture.

Polyamines are cationic molecules synthesized via a highly regulated pathway, obtained from the diet or produced by the gut microbiota. They are involved in general molecular and cellular phenomena that play a role also in vascular disease. Bicuspid aortic valve (BAV) is a congenital malformation associated to a greater risk of thoracic ascending aorta (TAA) aneurysm, whose pathogenesis is not yet well understood. We focused on differential analysis of key members of polyamine pathway and on polyamine concentration in non-dilated TAA samples from patients with either stenotic tricuspid aortic valve (TAV) or BAV (diameter ≤ 45 mm), vs. normal aortas from organ donors, with the aim of revealing a potential involvement of polyamines in early aortopathy. Changes of gene expression in TAA samples were evaluated by RT-PCR. Changes of ornithine decarboxylase 1 (ODC1), a key enzyme in polyamine formation, and cationic amino acid transporter 1 (SLC7A1/CAT-1) expression were analyzed also by Western blot. ODC1 subcellular localization was assessed by immunohistochemistry. Polyamine concentration in TAA samples was evaluated by HPLC. BAV TAA samples showed an increased concentration of putrescine and spermidine vs. TAV and donor samples, together with a decreased mRNA level of polyamine anabolic enzymes and of the putative polyamine transporter SLC7A1/CAT-1. The catabolic enzyme spermidine/spermine N1-acetyltransferase 1 showed a significant mRNA increase in TAV samples only, together with a decreased concentration of spermine. The decreased expression of SLC7A1/CAT-1 and ODC1 mRNAs in BAV corresponded to increased or unchanged expression of the respective proteins. ODC was located mainly in smooth muscle cell (SMC) nucleus in TAV and donor samples, while it was present also in SMC cytoplasm in BAV samples, suggesting its activation. In conclusion, BAV, but not TAV non-dilated samples show increased polyamine concentration, accompanied by the activation of a regulatory negative feedback mechanism.

The term \'epigenetics\' refers to heritable, reversible DNA or histone modifications that affect gene expression without modifying the DNA sequence. Epigenetic modulation of gene expression also includes the RNA interference mechanism. Epigenetic regulation of gene expression is fundamental during development and throughout life, also playing a central role in disease progression. The transforming growth factor β1 (TGF-β1) and its downstream effectors are key players in tissue repair and fibrosis, extracellular matrix remodelling, inflammation, cell proliferation and migration. TGF-β1 can also induce cell switch in epithelial-to-mesenchymal transition, leading to myofibroblast transdifferentiation. Cellular pathways triggered by TGF-β1 in thoracic ascending aorta dilatation have relevant roles to play in remodelling of the vascular wall by virtue of their association with monogenic syndromes that implicate an aortic aneurysm, including Loeys-Dietz and Marfan\'s syndromes. Several studies and reviews have focused on the progression of aneurysms in the abdominal aorta, but research efforts are now increasingly being focused on pathogenic mechanisms of thoracic ascending aorta dilatation. The present review summarizes the most recent findings concerning the epigenetic regulation of effectors of TGF-β1 pathways, triggered by sporadic dilative aortopathy of the thoracic ascending aorta in the presence of a tricuspid or bicuspid aortic valve, a congenital malformation occurring in 0.5-2% of the general population. A more in-depth comprehension of the epigenetic alterations associated with TGF-β1 canonical and non-canonical pathways in dilatation of the ascending aorta could be helpful to clarify its pathogenesis, identify early potential biomarkers of disease, and, possibly, develop preventive and therapeutic strategies.