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Acute aortic dissection is the most common life-threatening vascular disease, with sudden onset of severe pain and a high fatality rate. The pulsatile nature of blood flow exposes vascular smooth muscle cells (VSMCs) in the vessel wall to cyclic mechanical stretch (CMS), which evokes VSMC death, phenotypic switching, and migration, leading to aortic dissection. We have revealed that CMS of rat aortic smooth muscle cells (RASMCs) caused JNK- and p38-dependent cell death and that a calcium channel blocker, azelnidipine and an angiotensin II receptor antagonist, olmesartan decreased the phosphorylation of JNK and p38 and, subsequently, decreased cell death by CMS. JNK and p38 inhibitors also inhibited CMS-induced cell death. In addition, we showed that the expression of Cxcl1 and Cx3cl1 chemokines was induced by CMS in a JNK-dependent manner. Expression of Cxcl1 was also induced in VSMCs by hypertension produced by abdominal aortic constriction in mouse. In addition, antagonists against the receptors for CXCL1 and CX3CL1 increased cell death, indicating that CXCL1 and CX3CL1 protect RASMCs from CMS-induced cell death. We also revealed that STAT1 is activated in RASMCs subjected to CMS. Taken together, these results indicate that CMS of VSMCs induces inflammation-related gene expression, including that of CXCL1 and CX3CL1, and activates JNK and p38 MAP kinases, which may play important roles in the stress response against CMS caused by acute rise in blood pressure.

Objectives: Conventional biomaterials are not viable, do not grow, and do not provide contractile effects in cardiac tissue. Foreign synthetic material may become thrombogenic or infected. The most recent cardiac constructs consist of biodegradable material which has the potential to solve these problems. However, dynamic three-dimensional cell culture is necessary because conventional culture is limited to construct tough biografts., Methods: Vascular smooth muscle cells derived from rat aorta were seeded to poly-L-lactide-epsilon-capro-lactone copolymer in three groups; static culture group (static cell seeding + static cell culture), dynamic culture group (dynamic cell seeding + dynamic cell culture), and pre-seeding group [static cell seeding and culture for 1 week (pre-seeding) + dynamic cell culture]. The dynamic cell culture system used an original spinner flask. The pre-seeding technique used static cell seeding and culture before dynamic culture. The three groups were evaluated by cell proliferation and histologic studies., Results: Vascular smooth muscle cells could be proliferated in/on the biodegradable materials. The pre-seeding group cells grew much more efficiently than the other groups. Very few cells were found in the biodegradable materials with the dynamic groups. However, there were many cells in the materials with the static culture group and pre-seeding group, especially the pre-seeding group., Conclusions: Dynamic culture is useful for constructing tough biografts by the pre-seeding technique.

This clinical study was conducted to determine whether apoptosis is contributed to the occurrence of aortic dissection. The subjects comprised 11 patients who underwent Stanford type A aortic dissection and 4 autopsy cases, being the control group. The occurrence of apoptosis was determined by the TUNEL assay using an aortic wall specimen, and the distribution of macrophages and h-MMP-9 was examined by immunohistological staining. Apoptotic cells were observed in the aortic specimens for all of the 11 patients who underwent Standford type A aortic dissection, but not in any of the 4 autopsy cases. Moreover, apoptotic cells were present in large numbers on the surface of the false lumen strongly in 8 patients who underwent surgery within 1 month after aortic dissection, but not in 3 who underwent treatment after than 1 month. Those phenomena were also observed in the immunohistological staining of CD 68 and h-MMP-9. These findings indicate that apoptosis could be contributed to the occurrence of aortic dissection.

Endothelial cells of bovine brain microvascular vessels (BBECs), carotid artery (BCECs) and aorta (BAECs) were cultured on type I collagen and Matrigel. BBECs make tubular structures and BCECs and BAECs grow and make confluent monolayer on type I collagen gel. But BCECs and BAECs make tubular structures when second layer was overlaid. BBECs, BCECs and BAECs make tubular structures on Matrigel. These morphological changes were not affected by basic fibroblast growth factor. These results suggest that BBECs have more potent angiogenic ability than BCECs and BAECs.