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Aims Perivascular adipose tissue (PVAT) inhibits vascular smooth muscle cell (VSMC) contraction and stimulates VSMC proliferation by releasing protein factors. The present study was to determine whether visfatin is involved in these paracrine actions of PVAT, and if so, to explore the underlying mechanisms. Methods and results Visfatin was preferentially expressed in Sprague–Dawley rat and monkey aortic PVAT, compared with subcutaneous and visceral adipose tissues. The PVAT-derived visfatin was found to be a VSMC growth factor rather than a VSMC relaxing factor, which was proved by visfatin-specific antibody/inhibitor and direct observation of recombinant visfatin. Exogenous visfatin stimulated VSMC proliferation in a dose- and time-dependent manner via extracellular signal-regulated kinase (ERK 1/2) and p38 signalling pathways. This proliferative effect was further confirmed by enhancement of DNA synthesis and upregulation of proliferative marker Ki-67. Visfatin had no anti-apoptotic effect on normal cultured VSMCs, and it exerted an anti-apoptotic effect only during cell apoptosis induced by H2O2, excluding a role of anti-apoptosis in the visfatin-induced VSMC proliferation. Insulin receptor knockdown did not show any action on the visfatin effect. However, visfatin acted as a nicotinamide phosphoribosyltransferase to biosynthesize nicotinamide mononucleotide (NMN), which mediated proliferative signalling pathways and cell proliferation similar to the visfatin effect. Conclusion Visfatin stimulates VSMC proliferation via NMN-mediated ERK1/2 and p38 signalling. The present study provides a molecular link of visfatin to the paracrine action of PVAT, demonstrates a novel function of visfatin in promoting VSMC proliferation, and reveals NMN as a novel signalling molecule that triggers the proliferative process.

To study the dynamic changes and its clinical significance of integrated traditional Chinese and western medicine (TCM-WM) on IL-2 system, T cell and erythrocyte immune system in patients of lung cancer. Forty-eight patients with lung cancer were randomly divided into two groups: TCM-WM group (Group I ) and the chemotherapy group(Group II). The relevant immune indices, clinical symptoms and signs, changes of solid tumor and quality of life were dynamically observed and compared with those in 20 healthy subjects for control. The serum IL-2 level of lung cancer patients were originally significantly lower, while sIL-2R level higher than that of the healthy subjects. And they were raised and lowered respectively after treatment, especially in Group I, but still remained different from the control group yet. And there were highly negative correlation between IL-2 and sIL-2R levels. The percentage of CD3, CD4 and the CD4/CD8 ratio were decreased markedly in both groups. And the percentage of RBC-C3bRR was obviously lower, while that of RBC-ICR obviously higher. But the above-mentioned indices could be improved after treatment, especially in Group I, and there were highly positive correlation between CD4/CD8 ratio and RBC-C3bRR. However, in regard to the degree of improvement, the patients of Group I were in better position than those of Group II. At the same time, improvement of their clinical symptoms and signs, change of entity tumor and quality of life of Group I all proved to be better than those of Group II. The therapeutic superiority of TCM-WM on lung cancer may be related to the modulation on immune function. The effect of TCM-WM is better than that of chemotherapy alone.