HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors (statins) have been suggested to attenuate abdominal aortic aneurysm (AAA) growth. However, the effects of statins in human AAA tissues are not fully elucidated. The aim of this study was to investigate the direct effects of statins on proinflammatory molecules in human AAA walls in ex vivo culture. Simvastatin strongly inhibited the activation of nuclear factor (NF)-κB induced by tumor necrosis factor (TNF)-α in human AAA walls, but showed little effect on c-jun N-terminal kinase (JNK) activation. Simvastatin, as well as pitavastatin significantly reduced the secretion of matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-2 and epithelial neutrophil-activating peptide (CXCL5) under both basal and TNF-α-stimulated conditions. Similar to statins, the Rac1 inhibitor NSC23766 significantly inhibited the activation of NF-κB, accompanied by a decreased secretion of MMP-9, MCP-2 and CXCL5. Moreover, the effect of simvastatin and the JNK inhibitor SP600125 was additive in inhibiting the secretion of MMP-9, MCP-2 and CXCL5. These findings indicate that statins preferentially inhibit the Rac1/NF-κB pathway to suppress MMP-9 and chemokine secretion in human AAA, suggesting a mechanism for the potential effect of statins in attenuating AAA progression.

Critical limb ischemia (CLI) causes severe ischemic rest pain, ulcer, and gangrene in the lower limbs. In spite of angioplasty and surgery, CLI patients without suitable artery inflow or enough vascular bed in the lesions are often forced to undergo amputation of a major limb. Cell-based therapeutic angiogenesis has the potential to treat ischemic lesions by promoting the formation of collateral vessel networks and the vascular bed. Peripheral blood mononuclear cells and bone marrow-derived mononuclear cells are the most frequently employed cell types in CLI clinical trials. However, the clinical outcomes of cell-based therapeutic angiogenesis using these cells have not provided the promised benefits for CLI patients, reinforcing the need for novel cell-based therapeutic angiogenesis strategies to cure untreatable CLI patients. Recent studies have demonstrated the possible enhancement of therapeutic efficacy in ischemic diseases by preconditioned graft cells. Moreover, judging from past clinical trials, the identification of adequate transplant timing and responders to cell-based therapy is important for improving therapeutic outcomes in CLI patients in clinical settings. Thus, to establish cell-based therapeutic angiogenesis as one of the most promising therapeutic strategies for CLI patients, its advantages and limitations should be taken into account.

Background: Saphenous vein grafts (SVGs) are broadly used in coronary artery bypass grafting despite their inferior patency compared with arterial grafts. Recently, the no‐touch technique (NT), in which an SVG is harvested with a pedicle of perivascular adipose tissue (PVAT) without conduit distension, was shown to improve long‐term patency compared with conventional preparation (CV), wherein outer tissue is removed with distension. The NT was also reportedly associated with reduced atherosclerosis. Although endothelial damage provoked by conventional distension may underlie poor patency when CV is performed, the precise mechanisms underlying the salutary effects of the NT have been unclear. Methods and Results: Residual SVGs prepared with CV (CV‐SVGs) or NT (NT‐SVGs) were obtained during coronary artery bypass grafting. Nitric oxide (NO ₂ ⁻ /NO ₃ ⁻ (NO _x )) levels after 24 hours of tissue culture were quantified. The protein expression and localization were analyzed. The isometric force of SVG strips was measured. NT‐SVGs showed superior NO _x production to CV‐SVGs. PVAT generated the majority of NO _x in NT‐SVGs. PVAT highly expressed arginosuccinate synthase 1, a rate‐limiting enzyme in the molecular circuit for NO synthesis, thereby continuously providing the substrate for NO. A substantial level of endothelial NO synthase was also expressed in PVAT. Pharmacological inhibition of arginosuccinate synthase 1 or endothelial NO synthase significantly suppressed the NO _x production in NT‐SVGs. PVAT induced vasorelaxation through NO production, even in the endothelium‐denuded SVG strips. Conclusions: Preserving PVAT was predominantly involved in the superior NO _x production in NT‐SVGs. Since NO plays crucial roles in suppressing atherosclerosis, this mechanism may greatly contribute to the excellent patency in NT‐SVGs.

Elderly patients are sometimes denied aortic arch surgery because of the perception of poor outcomes and an unacceptable quality of life (QOL). In this study, we evaluated the early clinical outcomes, long-term survival and QOL following surgical treatment for aortic arch disease in octogenarian patients. A total of 47 consecutive patients over the age of 80 years were referred to our institutions. Of these patients, 20 underwent surgical intervention (surgical group) and 27 were treated medically (medical group). Kaplan–Meier survival analysis was performed between the two groups, and the results were compared with age-matched population data. The risk factors for mortality were determined using a Cox regression analysis. A QOL assessment was performed using the 36-item Short Form Health Survey. The patient characteristics at baseline were not significantly different between the two groups. In the surgical cases, conventional total aortic arch replacement was performed in 15 patients, debranched thoracic endovascular aortic repair (TEVAR) in 2 and chimney TEVAR in 3. Emergency procedures were performed in 3 patients. No hospital deaths occurred in the surgical groups. Reoperation for bleeding was required in 2 patients, and prolonged mechanical ventilation was required in 4 patients. The 5-year survival was 61.5% in the surgical group and 14.2% in the medical group (P = 0.02). Freedom from aorta-related death at 5 years was 92.3% in the surgical group and 32.3% in the medical group (P = 0.01). There were no differences in the 5-year survival between patients undergoing surgical intervention and the sex- and age-matched population (P = 0.80), whereas the 5-year survival was significantly lower in patients who received medical therapy relative to the sex- and age-matched population (P < 0.001). Medical therapy was the sole risk factor for mortality (hazard ratio: 3.16, P = 0.04). Among the survivors at mid-term, the quality-of-life measures were similar between those in the surgical group and those in the medical group. Surgical intervention for aortic arch disease in octogenarians can yield satisfactory early clinical outcomes and acceptable mid-term survival with adequate daily activity. This study indicates that among octogenarians, age alone should not disqualify a patient from receiving an aortic arch intervention.