We thank Tao Wu (Shandong University) for the average diameter, polydispersity index, and zeta potential measurements and Mr. Liu (Shandong University) for the transmission electron micrographs.
Hyperkinetic pulmonary arterial hypertension (PAH) severely influences the success of operation for congenital heart disease and deteriorates the prognosis of disease. Adipose-derived stromal cell (ADSC) is a good alternative multipotent stem cell for regeneration medicine. PAH rat models were established by arteriovenous shunt and ADSCs were isolated, cultured, and labeled in vitro. Twelve weeks after shunt operation, rats received an injection of 5 × 10(7) ADSCs. Two weeks after transplantation, hemodynamic abnormality induced by the shunt flow and the hypertrophy of right ventricle were reversed, which was confirmed by invasive measurement and echocardiography examination. The PAH rats receiving cell transplantation demonstrated decreased remodeling of small arteries in the lung; immunohistochemistry analysis showed augmented expression of hepatocyte growth factor (HGF) and increased number of pulmonary small arteries. Western blot and real-time reverse transcriptase-polymerase chain reaction indicated that the protein and mRNA levels of HGF and endothelial nitric oxide synthase increased, respectively, in the lung after cell transplantation. Our results suggested that ADSC transplantation can ameliorate PAH induced by shunt flow by enhancing the expression of HGF and subsequently promoting angiogenesis in the injured lung tissue.
Smoking is a major preventable risk factor for atherosclerosis. However, the causative link between cigarette smoke and atherosclerosis remains to be established. The objective of this study is to characterize the role of GTP cyclohydrolase 1 (GTPCH1), the rate‐limiting enzyme for de novo tetrahydrobiopterin (BH4) synthesis, in the smoking‐accelerated atherosclerosis and the mechanism involved. In vitro, human umbilical vein endothelial cells were treated with nicotine, a major component of cigarette smoke, which reduced the mRNA and protein levels of GTPCH1 and led to endothelial dysfunction. GTPCH1 overexpression or sepiapterin could attenuate nicotine‐reduced nitric oxide and ‐increased reactive oxygen species levels. Mechanistically, human antigen R (HuR) bound with the adenylateuridylate‐rich elements of the GTPCH1 3′ untranslated region and increased its stability; nicotine inhibited HuR translocation from the nucleus to cytosol, which downregulated GTPCH1. In vivo, nicotine induced endothelial dysfunction and promoted atherosclerosis in ApoE−/− mice, which were attenuated by GTPCH1 overexpression or BH4 supplement. Our findings may provide a novel and promising approach to atherosclerosis treatment.
We constructed a model mimicking the aberrant hemodynamic state in children with congenital heart disease with increased pulmonary blood flow to produce early characteristic morphology of hyperkinetic pulmonary hypertension. This method may provide an economic, easy, and stable animal model to study the mechanisms of pulmonary vascular remodeling in hyperkinetic pulmonary hypertension.
The present examination includes manufacture and portrayal of cryogel bio-composite implants containing chitosan-gelatin (CS-GT), cerium–zinc doped hydroxyapatite (CS-GT/Ce-Zn-HA) by cryogelation technique. The prepared cryogel biocomposites (CS-GT/HA and CS-GT/Ce-Zn-HA) were described by scanning electron microscope (SEM) and X-Ray diffraction (XRD) contemplates. The expansion of Ce-Zn in the CS-GT implants essentially expanded growing, diminished swelling, expanded protein sorption, and expanded bactericidal movement. The CS-GT/Ce-Zn-HA biocomposite had non-toxic towards rodent osteoblast cells. So the created CS-GT/Ce-Zn-HA biocomposite has favorable and potential applications over the CS-GT/HA platforms for bone tissue engineering.
EP ameliorates monocrotaline-induced PAH and reverses pulmonary vascular remolding in rats by inhibiting the release of TNF-α and IL-6 and reducing the expression of ET-1.
The common carotid artery and jugular vein anastomosis method is a stable hyperkinetic PAH model in rabbits. Reversible and irreversible PAH models were established at 3 and 6 months postoperatively, respectively.
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