The application discloses a kind of small-bore tissue engineeringblood vessel construction methods and artificial blood vessel.The construction method includes: obtaining ex vivovascular smooth muscle cells and preparing it into cell suspension;The cell suspension is inoculated on artificial blood vessel support and is carried out segmented culture, and the segmented culture includes: first-stage culture, second-stage culture, third-stage culture;The first-stage culture uses first culture medium;The second-stage culture uses second culture medium;The third-stage culture uses third culture medium;The construction method provided by the application has the advantages of simple equipment, low cost, convenient operation, can realize high-throughput parallel culture and significantly shorten the culture cycle, provides efficient, feasible new scheme for the scale preparation and clinical application of small-bore tissue engineering blood vessel.
The application discloses a blood pressure calculation method and equipment based on cross-scale fluid-solidcoupling and considering nonlinear biomechanical characteristics of an aorta, and the method comprises the following steps: establishing a three-dimensional ideal aorta geometric model; establishing a zero-dimensional heart lumped parameter model to simulate the process that the heart pumps blood to the aorta inlet through periodic contraction and diastole; establishing a zero-dimensional three-element Windkessel model of small arteries to simulate blood flowmicrocirculation of peripheral small arteries; establishing a blood vessel wall biomechanical model containing residual stress of the aorta wall and active contraction of smooth muscle cells to obtain a pressure-radius relationship of the aorta wall as a fluid wall boundary condition to simulate the change process of the aorta radius in blood circulation; and coupling the three-dimensional ideal geometric model of the aorta, the zero-dimensional heart lumped parameter model and the zero-dimensional three-element Windkessel model to construct a cross-scale fluid-solidcouplingsystem of hemodynamics, and the blood pressure in the aorta is calculated through iterative solution.
In particular, compositions comprising iPSC-derived parietal cell precursors (iMPCs) generated using NK3 homeobox 1 (NKX3.1; parietal cell fate-determining transcription factor) and methods for their preparation and use are described herein. In addition, in particular, methods for maturing iMPCs into functional parietal cell subtypes, including smooth muscle cells, perivascular cells, and fibroblasts, as well as methods for increasing angiogenesis, angiogenesis, and cell junctions, are described herein. iMPCs mediate the formation of functional blood vessels when transplanted together with endothelial cells (ECs); thus, methods for modeling vascular diseases (e.g., 3D vascular organoids (VOs)) and therapeutic vascularization, comprising a method of administering iMPCs and ECs and a step of administering iMPCs and ECs, are also described herein.
The application belongs to the technical field of biological medicine and nanomaterials, and particularly relates to a nano system for targeted photothermal-chemotherapy synergistic treatment of abdominal aortic aneurysm as well as a preparation method and application thereof. The system is a mesoporous polydopamine-coated gold nanorod cluster (AuM) nanoparticle co-loaded with one or more traditional Chinese medicine ingredients and modified by c(RGDfK) cyclic peptide. The preparation comprises the following steps: taking chloroauric acid and dopaminehydrochloride as raw materials, synthesizing AuM in the presence of a reaming agent and a template agent by a one-step method; further loading a large amount of drugs in the mesopores to obtain drug-loaded nanoparticles; and finally grafting a targeting peptide on the surface of the nanoparticles to obtain the final product. The system has the characteristics of targeting macrophages and smooth muscle cells, NIR-Ⅱ photothermal conversion and photothermal response drug release. The in-vitro and in-vivo experimental results show that the system can realize local photothermal treatment and precise drug release under NIR-Ⅱ light, and inhibit aortic dilation through various cell behaviors, thereby providing a nano preparation with clinical transformation potential for precise treatment of abdominal aortic aneurysm.
The application belongs to the technical field of genetic engineering and cardiovascular disease treatment, and specifically discloses application of an expression inhibitor of a TSPAN4 gene in preparation of a drug for treating cardiovascular diseases and the drug containing the expression inhibitor of the TSPAN4 gene. The application first constructs a carotid artery injury mouse model, and research finds that the expression absence of TSPAN4 has a significant improvement effect on intimal neogenesis. Further, the expression of the TSPAN4 gene is inhibited through siRNA interference RNA technology targeting the TSPAN4 gene, and it is found that after being treated by human h-siTSPAN4, the phenotype of smooth muscle cells can be changed, and the purpose of treating cardiovascular diseases can be achieved. The method of the application can inhibit the expression of the TSPAN4 gene by delivering siRNA, so as to inhibit the proliferation and migration of abnormal smooth muscle cells and reduce the development of cardiovascular diseases.
The application provides use of a trisaccharide compound with a core structure of GlcN(1→4)IdoA(1→4)GlcNS in preparation of a drug for treating or preventing pulmonary arterial hypertension, which can effectively improve right ventricular hypertrophy, right ventricular function damage and hemodynamic parameters of an animal model of the pulmonary arterial hypertension, delay or improve excessive proliferation of arterial endothelial cells and smooth muscle cells in the pulmonary arterial hypertension, treat vascular remodeling and vascular muscularization of a pulmonary arterial hypertension patient, and has a good protective effect on a heart in the pulmonary arterial hypertension.
A use of a trisaccharide compound having a core structure of GlcN(1→4)IdoA(1→4)GlcNS in the preparation of a drug for treating or preventing pulmonary hypertension. The drug can effectively alleviate right ventricular hypertrophy and right ventricular dysfunction and optimize hemodynamic parameters in an animal model of pulmonary hypertension, slow down or ameliorate excessive proliferation of arterial endothelial cells and smooth muscle cells in pulmonary hypertension, treat vascular remodeling and vascular muscularization in patients with pulmonary hypertension, and has a good protective effect on a heart in pulmonary hypertension.
This invention belongs to the field of biomedical technology and discloses the application of the small moleculetripeptide Ser-Ser-Cys (SSC) in inhibiting the phenotypic transformation of vascular smooth muscle cells (VSMCs). SSC is an endogenous differentially expressed tripeptide screened and identified from the serum of hypertensive non-atherosclerotic patients using non-targeted metabolomics technology. In vitro experiments show that SSC can effectively inhibit angiotensin II (Ang II)-induced abnormal proliferation, migration, and phenotypic transformation from contractile to synthetic VSMCs. Its mechanism of action is related to the regulation of the Keap1 / Nrf2 signaling pathway, improvement of cellular oxidative stress, and mitochondrial function. This invention provides a new approach for using SSC in the preparation of drugs or functional foods for the prevention and treatment of hypertension-related vascular remodeling.
The present application belongs to the technical field of medicine, and particularly relates to a pharmaceutical composition and use thereof. The pharmaceutical composition composed of a PGI2 receptoragonist compound or a pharmaceutical salt thereof and bosentan has a synergistic effect on inhibiting K+ induced pulmonary artery ring tension increase and / or inhibiting PDGF induced human pulmonary arterysmooth musclecell proliferation. The combined pharmaceutical composition is more helpful for treating the disease of a patient with pulmonary arterial hypertension which cannot be controlled by a single drug. The combined pharmaceutical composition has a stronger synergistic effect on inhibiting K+ induced pulmonary artery ring tension increase and / or inhibiting PDG induced human pulmonary arterysmooth musclecell proliferation than the combined use of the existing drug selexipag and bosentan at a specific ratio and test concentration. Therefore, the combined pharmaceutical composition at a specific ratio and test concentration is more helpful for treating the disease of a patient with moderate to severe pulmonary arterial hypertension which cannot be controlled by the combined use of the existing drug selexipag and bosentan.
This invention discloses a recombinant geneexpression vector and its use in the preparation of drugs for treating pulmonary arterial hypertension (PAH). The vector contains a nucleotide sequence encoding a small activating RNA (saRNA), which specifically targets and upregulates the expression of the endogenous Ste20-like kinasegene. Based on the discovery that SLK gene expression is significantly downregulated in vascular smooth muscle cells of PAH, this invention utilizes an RNA activation mechanism to activate the transcription and expression of the endogenous SLK gene by delivering specific saRNA to the lesion site. The vector can employ a vascular smooth musclecell-specific promoter and an optimized miRNA backbone to achieve tissue-specific and highly efficient expression. The recombinant vector of this invention effectively inhibits the excessive proliferation and migration of pulmonary arterysmooth muscle cells, alleviates right ventricular hypertrophy, reverses pulmonary vascular remodeling, and significantly reduces pulmonary artery pressure, providing a novel target and gene therapy strategy for the clinical treatment of PAH.
This invention belongs to the field of biomedical technology and discloses the application of calcium-activated chloride channel AN01 / TMEM16A in the prevention and treatment of atherosclerosis. This invention also discloses the application of ANO1 promoters in the preparation of drugs for the treatment or prevention of atherosclerosis. Through research, this invention has found that the loss of ANO1 in vascular smooth muscle cells exacerbates the instability of atherosclerotic plaques, while overexpression of ANO1 can enhance the stability of atherosclerotic plaques and delay the progression of atherosclerosis. ANO1 in smooth muscle cells is one of the key drivers of atherosclerosis progression. This invention clarifies that targeting the non-ion channel function of ANO1 protein has important clinical translational value for screening drugs for the treatment or prevention of atherosclerosis.
This invention discloses a vascular graft that maintains the contractile phenotype of smooth muscle cells and its preparation method. The vascular graft is modified with a polydopamine coating on its luminal surface, anchoring RGD / CD47 dual-modified lipid nanoparticles, which encapsulate mRNA encoding olarumab. After implantation, the dual-modified LNPs specifically target endothelial cells, achieving highly efficient transfection and enabling endothelial cells to continuously secrete olarumab in situ, thereby blocking the PDGF-BB / PDGFR-α signaling pathway, maintaining the contractile phenotype of smooth muscle cells, and significantly inhibiting restenosis and calcification of the vascular graft. Experiments show that the dual-modified LNPs have a transfection efficiency of >90% in endothelial cells, exhibiting an unexpected synergistic effect of cell-selective delivery.