GDF-5/7 and bFGF activate integrin alpha2-mediated cellular migration in rabbit ligament fibroblasts.

Cellular activities responding to growth factors are important in ligament healing. The anterior cruciate ligament (ACL) has poor healing potential compared to the medial collateral ligament (MCL). To assess the differences, we investigated the proliferation, migration, adhesion, and matrix synthesis responding to growth factors in rabbit ACL and MCL fibroblasts. ACL cell proliferation to basic fibroblast growth factor (bFGF), bone morphogenetic protein-2, growth and differentiation factor (GDF)-5, and GDF-7 treatment was similar to that of MCL cells. GDF-5 enhanced Col1a1 expression in ACL and MCL fibroblasts up to 4.7- and 17-fold levels of control, respectively. MCL fibroblasts showed stronger migration activities in response to bFGF and GDF-5 than ACL cells. GDF-5/7 and bFGF also changed the stress fiber formation and cellular adhesion by modulating the distribution of integrin alpha2. Functional blocking analyses using anti-integrin alpha2 antibodies revealed that cellular migration responding to growth factors depended on the integrin alpha2-mediated adhesion on type I collagen. The expression of integrin alpha2 was also increased by growth factors in both cells. Our results demonstrate that GDF-5/7 and bFGF stimulate cellular migration by modulating integrin alpha2 expression and integrin alpha2-dependent adhesion, especially in MCL fibroblasts. These findings suggest that the different healing potential between ACL and MCL may be caused by different cellular behavior in the integrin alpha2-mediated cellular migration in response to growth factors.

Disease-specific screening for deep venous thrombosis and pulmonary thromboembolism using plasma D-dimer values after total knee arthroplasty.

We prospectively evaluated the disease-specific features of the early postoperative plasma D: -dimer value and the relationship with deep venous thrombosis and/or pulmonary thromboembolism (DVT/PE) in 95 patients following total knee arthroplasty. Patients in whom DVT/PE was highly suspected were diagnosed by high-resolution multi-detector row computed tomography scanning (MDCT). Forty-nine knees in 46 patients with rheumatoid arthritis (RA, 24 knees) or osteoarthritis (OA, 25 knees) were finally recruited. DVT/PE was detected in 28 (57.1%) of the 49 cases examined by diagnostic MDCT: 12 (50.0%) of the 24 cases of RA, and 16 (64.0%) of the 25 cases of OA. Of these, PE was found in 11 cases (39.2%), but none of them showed clinical symptomatic signs of dyspnea or chest pain. In both RA and OA cases, there were statistically significant differences in the D: -dimer value on postoperative day 3 (P = 0.027) and after day 28 (P = 0.037) between the groups with and without DVT/PE. In OA cases, there were significant differences between the two groups on postoperative days 1 (P = 0.034), 3 (P = 0.020), 5 (P = 0.005), and 7 (P = 0.045), respectively. At the baseline, perioperative D: -dimer levels in the RA group without DVT/PE were higher than in the OA group. However, multivariate logistic regression analysis showed that RA was not a significant risk factor of DVT/PE in comparison with OA. In conclusion, individual evaluation of the D: -dimer level between RA and OA should provide a more precise predictive indicator of early postoperative DVT/PE.

Influence of coronary artery disease risk factors on baroreflex sensitivity in the elderly.

In this study, we assessed whether baroreflex sensitivity (BRS) is influenced by risk factors of cardiovascular disease. Subjects of this study were 95 elderly people (40 males and 55 females; mean age +/- SD, 66.6+/-1.6 years) who underwent a medical check-up. BRS was determined as the gain of transfer function in baroreflex arc by spectral analysis of mean blood pressure and R-R interval variabilities in low-frequency band (0.04-0.15 Hz). Gender-related differences in BRS and relationships between BRS and various risk factors of cardiovascular disease were investigated. The value of BRS was significantly higher in males [10.7+/-3.7 (SD) ms/mmHg] than in females [9.0+/-4.0 ms/mmHg, p< 0.05]. However, this gender-related difference disappeared when other variables were taken into account in the multivariate model. Multiple regression analyses showed independent inverse relationships between BRS and heart rate [b=-0.016+/-0.004 (SE) bpm, beta=-0.39], and between BRS and platelet count [b=-0.002+/-0.001 x 103/ micro l, beta=-0.22]. Our results indicated that BRS is inversely related to platelet count in the elderly population. The precise mechanism of this correlation is unknown, but platelet factors released from platelet aggregates can potentially influence vascular function and modify BRS, or there is a common underlying determinant responsible for the covariation.

Effect of plasma lipoproteins on natural killer cell activity in the elderly population.

BACKGROUND: Natural killer (NK) cells possess spontaneous cytotoxicity against tumors and virus-infected cells to play a major role in immunosurveillance and defense against the development of cancer, as well as bacterial and viral infections. The role of plasma lipoproteins in atherogenesis is well recognized, but the physiological relevance of their immunoregulatory properties is still questioned. In particular, it is unknown whether hypercholesterolemia should be considered a risk factor for diminished immunity in old age. METHODS: To evaluate effects of plasma lipoprotein levels on immune function, we assessed the relation between plasma lipoprotein profiles and NK cell activity. NK cell activity was assayed by release of (51)Cr from K562 target cells, and concurrent plasma lipoprotein levels were measured in 47 samples of elderly males (mean age +/- SD, 66.6 +/- 1.7 years). RESULTS: Univariate regression analyses revealed direct relations between NK cell activity and high-density lipoprotein cholesterol (r=.46, p<.001), apolipoprotein (Apo) A-1 (r=.48, p<.001), and Apo A-2 (r=.46, p<.005). In addition, multiple regression analyses showed a direct independent relation between NK cell activity and Apo A-1 (b=0.32+/-0.09 mg/dl, beta=0.48, and p <.001). CONCLUSION: NK cell activity is related directly to plasma Apo A-1 levels in elderly subjects. The mechanisms of this interaction are unknown, but Apo A-1 contributes to the composition of the antiatherogenic fraction of high-density lipoprotein and could also defend against infectious and malignant disease through a potential for NK cell activity.