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Outline
Currently, endovascular interventional therapy represents the primary clinical approach for vascular lesions. Restenosis caused by mechanical procedures, however, has become increasingly prominent. This study aimed to explore the feasibility and underlying mechanisms of naked plasmid encoding hepatocyte growth factor (HGF) for preventing post-interventional luminal restenosis through a rat animal model and in vitro experiments.
① A rat carotid artery injury model was established by pulling inflated balloon. Eighteen male SD rats (6 to 8 weeks old, weighing 260 to 280 g) were randomly divided into a sham operation group, normal saline group, and HGF group (adentitial injection of HGF naked plasmid) (n=6 for each group). Peak systolic velocity was measured using carotid ultrasound, and the area of the vascular intima and HGF expression were assessed through HE staining and HGF immunofluorescence staining, respectively. The expression levels of phenotypic markers in the carotid media were determined by Western blotting. ② Vascular endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) were obtained from rat carotid arteries through primary culture, and both ECs and VSMCs were transfected with the plasmids haboring HGF. The proliferative and migratory abilities of transfected and untransfected ECs were assessed through CCK-8 assay and cell scratch assay, respectively. After Ang Ⅱ-induced VSMC transformation, the effects of Ang Ⅱ induction alone, Ang Ⅱ induction followed by HGF plasmid transfection, Ang Ⅱ induction followed by exogenous HGF treatment on VSMC migratory ability were detected by cell scratch assay, and the expression levels of phenotypic markers in VSMCs were determined by RT-qPCR and Western blotting.
① Animal experiments showed that, compared with the normal saline group, the peak systolic velocity of the carotid artery in the HGF group was significantly lower on post-injury day 3 and day 7 (day 3: 422.62±16.99 vs 1 050.58±40.92 mm/s; day 7: 631.81±26.11 vs 1 309.78±73.13 mm/s; P<0.001), the increase in carotid artery intimal area was significantly less (day 3: 0.16±0.03 vs 0.83±0.09 mm²; day 7: 0.17±0.03 vs 1.15±0.31 mm²; P<0.001), the green fluorescence intensity of HGF in the carotid artery tissue was significantly higher (P<0.001), and the protein expression levels of synthetic phenotype markers vimentin, OPN, and PCNA were all significantly lower (P<0.001), whereas the protein expression level of contractile phenotype marker α-SMA was comparable (P>0.05). ② Cell experiment results showed that, compared with untransfected ECs, HGF plasmid-transfected ECs exhibited significantly enhanced proliferative activity and migratory ability (P<0.05). Compared with VSMCs receiving Ang Ⅱ induction alone, both Ang Ⅱ-induced VSMCs subsequently transfected with HGF plasmid and those treated with exogenous HGF demonstrated significantly reduced migratory ability (P<0.01), significantly decreased mRNA and protein expression levels of the synthetic phenotype marker vimentin (P<0.05), and significantly elevated mRNA and protein expression levels of the contractile phenotype marker SM-MHC (P<0.05).
HGF may promote vascular re-endothelialization and inhibit intimal hyperplasia by enhancing the proliferative and migratory abilities of vascular ECs and inhibiting the transition of VSMCs to a synthetic phenotype.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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