Gaoke Feng

Hepatocyte growth factor regulates the TGF‑β1‑induced proliferation, differentiation and secretory function of cardiac fibroblasts

Cardiac fibroblast (CF) proliferation and transformation into myofibroblasts play important roles in cardiac fibrosis during pathological myocardial remodeling. In this study, we demonstrate that hepatocyte growth factor (HGF), an antifibrotic factor in the process of pulmonary, renal and liver fibrosis, is a negative regulator of cardiac fibroblast transformation in response to transforming growth factor-β1 (TGF-β1). HGF expression levels were significantly reduced in the CFs following treatment with 5 ng/ml TGF-β1 for 48 h. The overexpression of HGF suppressed the proliferation, transformation and the secretory function of the CFs following treatment with TGF-β1, as indicated by the attenuated expression levels of α-smooth muscle actin (α-SMA) and collagen I and III, whereas the knockdown of HGF had the opposite effect. Mechanistically, we identified that the phosphorylation of c-Met, Akt and total protein of TGIF was significantly inhibited by the knockdown of HGF, but was significantly enhanced by HGF overexpression. Collectively, these results indicate that HGF activates the c-Met-Akt-TGIF signaling pathway, inhibiting CF proliferation and transformation in response to TGF-β1 stimulation.

Effect of novel bioresorbable scaffold composed of poly-l-lactic acid and amorphous calcium phosphate nanoparticles on inflammation and calcification of surrounding tissues after implantation

To study the effect of novel bioresorbable scaffold composed of poly-L-lactic acid (PLLA) and amorphous calcium phosphate (ACP) nanoparticles on inflammation and calcification of surrounding tissues after implantation. Ninety six PLLA/ACP scaffolds and 96 PLLA scaffolds were randomly implanted in the back muscle tissue of 48 SD rats. At the 1st, 2nd, 4th, and 12th weeks after implantation, the calcium, phosphorus, and alkaline phosphatase levels in the blood serum and the contents of calcium and alkaline phosphatase in the tissue surrounding the scaffolds were measured. Hematoxylin-eosin staining was performed to count the inflammatory cells. Von kossa staining was performed to observe calcification of the surrounding tissue around the scaffold. NF-κB staining was performed by immunohistochemistry to calculate the positive expression index of inflammatory cells. Western blot was used to detect the expression of IL-6 and BMP-2 in the tissues surrounding the scaffolds. At the 1st, 2nd, 4th, and 12th weeks after scaffold implantation, there were no significant difference in the serum concentration of calcium, phosphorus, alkaline phosphatase and in the tissue homogenate concentration of alkaline phosphatase between the two groups (P > 0.05). The level of calcium in tissue homogenates was lower in the PLLA/ACP group than in the PLLA group at 12-week (P < 0.05). The hematoxylin-eosin staining results showed that the inflammatory cell count in the PLLA/ACP group was lower than the PLLA group at 4-week and 12-week (P < 0.05). The results of NF-kB positive expression index showed that the PLLA group was significantly more than the PLLA/ACP group at 4-week and 12-week (P < 0.01). Western blot results showed that IL-6 expression levels in the PLLA/ACP group scaffolds were significantly lower than those in the control group at the 2-week, 4-week and 12-week (P < 0.05). The expression of BMP-2 in the PLLA group was significantly lower than that in the control group at 4-week and 12-week (P < 0.05). The PLLA/ACP composite material has good histocompatibility. The integration of nanoscale ACPs reduces the inflammatory response induced by acidic metabolites of PLLA material and may inhibit tissue calcification by reducing the amount of calcification factors in the body.

Six-month evaluation of novel bioabsorbable scaffolds composed of poly-L-lactic acid and amorphous calcium phosphate nanoparticles in porcine coronary arteries

Objective Using coronary angiography and intravascular ultrasound methods to evaluate the performance of the novel fully bioabsorbable scaffold (NFBS) composed of poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) at six-month follow-up by comparing with PLLA scaffolds Methods Twelve PLLA/ACP scaffolds and 12 PLLA scaffolds were implanted into the coronary arteries of 12 miniature pigs. Quantitative coronary angiography (QCA) was used to measure the reference vessel diameter (RVD), mean lumen diameter (MLD) and late lumen loss (LLL). According to IVUS images, we calculated the strut malapposition rate (SMR) at post implantation, strut overlap rate (SOR), reference vessel area (RVA), mean stent area (MSA), mean lumen area (MLA) and luminal patency rate (LPR) at six-month follow-up. The radial strength of the scaffold was evaluated using a catheter tensile testing machine. Results QCA results indicated that, at six month, MLD of PLLA/ACP scaffolds was greater than those of PLLA scaffolds (2.47 ± 0.22 mm vs. 2.08 ± 0.25 mm, P < 0.05); LLL of PLLA/ACP scaffolds was less than those of PLLA scaffolds (0.42 ± 0.20 mm vs. 0.75 ± 0.22 mm, P < 0.05). IVUS results showed the SMR and SOR were all significantly less with the PLLA/ACP scaffolds than the PLLA scaffolds (5.84% ± 3.56% vs. 17.72% ± 4.86%, P < 0.05) (6.17% ± 4.63% vs. 17.65% ± 4.29%, P < 0.05). MSA, MLA and LPR of the PLLA/ACP scaffolds were all greater than those of PLLA scaffolds (6.35 ± 0.45 mm2 vs. 5.35 ± 0.51 mm2, P < 0.05) (4.76 ± 0.46 mm2 vs. 3.77 ± 0.46 mm2, P < 0.05) (78.01% ± 12.29% vs. 61.69% ± 9.76%, P < 0.05). Radial strength of PLLA/ACP scaffold at six month was greater than that of PLLA scaffold (76.33 ± 3.14 N vs. 67.67 ± 3.63 N). Conclusion The NFBS had less stent recoil, better lumen patency rate and greater radial strength than PLLA scaffolds. The results suggest the NFBS scaffolds can maintain the structural strength and functional performance, which are effective for up to six months when implanted in porcine coronary arteries.