Is Human-induced Pluripotent Stem Cell the Best Optimal? / 中华医学杂志(英文版)

<p><b>Objective</b>Since the advent of induced pluripotent stem cell (iPSC) technology a decade ago, enormous progress has been made in stem cell biology and regenerative medicine. Human iPSCs have been widely used for disease modeling, drug discovery, and cell therapy development. In this review, we discuss the progress in applications of iPSC technology that are particularly relevant to drug discovery and regenerative medicine, and consider the remaining challenges and the emerging opportunities in the field.</p><p><b>Data Sources</b>Articles in this review were searched from PubMed database from January 2014 to December 2017.</p><p><b>Study Selection</b>Original articles about iPSCs and cardiovascular diseases were included and analyzed.</p><p><b>Results</b>iPSC holds great promises for human disease modeling, drug discovery, and stem cell-based therapy, and this potential is only beginning to be realized. However, several important issues remain to be addressed.</p><p><b>Conclusions</b>The recent availability of human cardiomyocytes derived from iPSCs opens new opportunities to build in vitro models of cardiac disease, screening for new drugs and patient-specific cardiac therapy.</p>

A Preliminary Study of the Therapeutic Role of Human Early Fetal Aorta-derived Endothelial Progenitor Cells in Inhibiting Carotid Artery Neointimal Hyperplasia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Endothelial cell damage is an important pathophysiological step of restenosis after angioplasty and stenting. Cell transplantation has great therapeutic potential for endothelial recovery. We investigated the effect of transplanting endothelial progenitor cells (EPCs) derived from human early fetal aortas in rat injured arteries.</p><p><b>METHODS</b>The carotid arterial endothelium of Sprague-Dawley rats was damaged by dilatation with a 1.5 F balloon catheter, and then EPCs derived from human early fetal aortas (<14 weeks) were injected into the lumen of the injured artery in transplanted rats, with an equal volume of normal saline injected into control rats. Rats were sacrificed at 2 and 4 weeks after treatment and transplanted cells were identified by immunohistochemical staining with anti-human CD31 and anti-human mitochondria antibodies. Arterial cross-sections were analyzed by pathology, immunohistochemistry, and morphometry.</p><p><b>RESULTS</b>Green fluorescence-labeled EPCs could be seen in the endovascular surface of balloon-injured vessels after transplantation. The intimal area and intimal/medial area ratio were significantly smaller in the transplanted group than in the control (P < 0.05) and the residual lumen area was larger (P < 0.05). After EPC transplantation, a complete vascular endothelial layer was formed, which was positive for human von Willebrand factor after immunohistochemical staining, and immunohistochemical staining revealed many CD31- and mitochondria-positive cells in the re-endothelialized endothelium with EPC transplantation but not control treatment.</p><p><b>CONCLUSION</b>EPCs derived from human early fetal aorta were successfully transplanted into injured vessels and might inhibit neointimal hyperplasia after vascular injury.</p>

Effect of two Chinese medicinal compounds, blood-activating and water-draining medicine, on tumor necrosis factor α and nuclear factor κ B expressions in rats with intracerebral hemorrhage / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of blood-activating Chinese medicinal compounds and water-draining Chinese medicinal compounds on tumor necrosis factor alpha (TNF-α) and nuclear factor kappaB (NF-κ B) expressions in rats with intracerebral hemorrhage (ICH) at the acute stage, and to monitor their therapeutic effect and mechanism of action on inflammation and cerebral edema.</p><p><b>METHODS</b>A rat model of cerebral hemorrhage was achieved by injecting autologous arterial blood into the caudate nucleus. A total of 168 rats were randomly divided into 4 groups: blood-activating medicine group (n=42), water-draining medicine group (n=42), sham operated group (n=42), and the model group (n=42). A series of brain samples were obtained at days 1, 3 and 5 after ICH from rats in all groups. Protein expression levels of TNF-α and NF-κ B were measured by immunohistochemical staining and gene expression levels of TNF-α and NF-κ B were measured by real-time fluorescent PCR.</p><p><b>RESULTS</b>Compared to the sham operated group, protein expression levels of TNF-α and NF-κ B in the model group significantly increased (P<0.01). Protein and gene expressions of TNF-α from the blood-activating medicine group and water-draining medicine group significantly decreased when compared to those in the model group P<0.05). Meanwhile, compared to the model group, the expression of NF-κ B in the blood-activating medicine group significantly decreased (P<0.05), while expression of NF-κ B in the water-draining medicine group did not differ (P>0.05).</p><p><b>CONCLUSIONS</b>Blood-activating Chinese medicinal compounds and water-draining Chinese medicinal compounds can alleviate inflammation of peripheral tissue and cerebral edema. However, the blood-activating Chinese medicinal compounds were more effective than the water-draining Chinese medicinal compounds. The possible effective mechanism may be by means of inhibiting the activation of NF-κ B so as to suppress the transcription of target genes including gene expression of TNF-α.</p>

ADAMTS-1 expression in rat myocardium after ischemic preconditioning: age-associated differences / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been found that cardiac protection afforded by ischemic preconditioning (IPC) is significantly reduced in the senescent myocardium. ADAMTS-1 (a disintesrin and metalloprotease with thrombospondin type 1 motifs) has been shown to inhibit angiogenesis in a variety of in vitro and in vivo assays. The aim of this study was to investigate the age-associated differences in ADAMTS-1 protein expression in rat myocardium after ischemic preconditioning.</p><p><b>METHODS</b>Sixty-four young (4 months) and old (24 months) male Sprague-Dawley rats were randomly assigned to an IPC group (40 rats) or a sham group (rats). A model of delayed IPC was induced and rats were sacrificed and myocardial samples were harvested from the ischemic-reperfused region for immunohistochemical detection of ADAMTS-1 at serial time points after IPC. A model of myocardial infarction was produced by ligation of the left anterior descending coronary artery in additional sets of young and old rats after sham or IPC procedures, then age-associated myocardial infarction survival after IPC was calculated.</p><p><b>RESULTS</b>ADAMTS-1 expression increased significantly in old rats compared to young rats (P < 0.05). The mean densities of ADAMTS-1 protein at 0, 6, 12, and 24 hours in young-IPC group after IPC were 0.05 ± 0.01, 0.13 ± 0.03, 0.16 ± 0.04, and 0.12 ± 0.03 vs. 0.07 ± 0.03, 0.20 ± 0.03, 0.24 ± 0.05, and 0.21 ± 0.04 in old-IPC group. IPC resulted in diminished survival rates (5/35 vs. 6/14, old-IPC group vs. old-sham group, P < 0.05), reduced left ventricular fractional shortening ((13.9 ± 2.8)% vs. (18.3 ± 2.3)%, P < 0.05) and increased the myocardial infarction size ((37.9 ± 3.2)% vs. (32.8 ± 5.1)%, P < 0.05) in the older rats.</p><p><b>CONCLUSIONS</b>Cardioprotection with IPC is attenuated in the older heart. ADAMTS-1 expression induced by IPC is greater in old rats. Over-expression of anti-angiogenic factors might be a potential mechanism behind reduced protection after IPC associated with aging.</p>

Effect of ischemia preconditioning on pro- and anti- angiogenic molecule expression and functional arteries formation / 中华心血管病杂志

<p><b>OBJECTIVE</b>to observe the effect of ischemia preconditioning (IPC) on the expression of pro-angiogenic VEGF, PDGF and anti-angiogenic ADAMTS-1, and arteriogenesis.</p><p><b>METHODS</b>rat heart IPC model was made by 4 circles of occluding the LAD for 6 min followed by 6 min of reperfusion. The expression of VEGF, PDGF-B and ADAMTS-1 in the ischemic area was examined with immunohistochemistry at 6, 12 and 24 h after IPC. IPC plus myocardial infarction model was induced by LAD ligation 24 h after IPC, 14 days later, the anti-SM-α-actin antibody was used to detect the mature neovascularization in the border of the infracted area.</p><p><b>RESULTS</b>VEGF, PDGF-B and ADAMTS-1 were significantly upregulated in the ischemic area in IPC group compared with the control group (P < 0.05). Density of mature arteries was also significantly increased in IPC plus MI group than that in MI group (P < 0.05).</p><p><b>CONCLUSION</b>IPC promoted the formation of mature new arteries which may be modulated by upregulating VEGF, PDGF-B, and ADAMTS-1 expressions.</p>

Ischemia preconditioning attenuated myocardial ischemia via upregulating the expression of adiponectin in rat / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate whether adiponectin plays a role in the protection of myocardium in the rat myocardial ischemia preconditioning (IPC) model.</p><p><b>METHOD</b>Infarct size was measured by Masson's Trichrome staining, the expression of protein and mRNA of adiponectin at 0, 6, 12 and 24 h after IPC was examined by immunohistochemistry and quantitative real time RT-PCR, plasma levels of adiponectin at above mentioned four time points after IPC were detected by ELISA in IPC and MI rats.</p><p><b>RESULT</b>Infarct size was smaller in IPC than in MI rats (20% ± 2% vs. 31% ± 3%, P < 0.05). The expression of adiponectin mRNA at 6 h and 12 h after IPC was 2.2 and 2.1 times higher than in Sham rats at respective time points (P < 0.05). Immunohistochemistry staining evidenced increased adiponectin expression in the ischemic area and weak expression of adiponectin in non-ischemic area (P < 0.05). Compared to the sham group, the plasma level of adiponectin increased significantly at 0, 6 and 12 h after IPC (0 h: 7.40 ± 0.47 vs. 10.90 ± 1.74; 6 h: 8.18 ± 1.41 vs. 10.98 ± 1.74; 12 h: 6.97 ± 1.02 vs. 9.31 ± 0.96, P < 0.05).</p><p><b>CONCLUSION</b>IPC reduced infarction size, upregulated the myocardial expression of adiponectin at mRNA and protein levels, and increased plasma adiponectin concentration, suggesting that the adiponectin may play a critical role in the protective effect of IPC.</p>

Effects of perindopril and enalapril on atherosclerosis development of apolipoprotein E knockout mice / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the effects of perindopril and enalapril on the development of atherosclerotic lesions in ApoE knockout mice.</p><p><b>METHODS</b>ApoE knockout mice were treated with perindoprilor (1.5 mg.kg(-1).d(-1), n = 20), enalapril (7.5 mg.kg(-1).d(-1), n = 20) or saline (0.2 ml saline/d, n = 20) per gavage for 20 weeks. Blood pressure and lipids were measured at the study end. Aortic root atherosclerotic plaque was then quantified and the content of collagen and the size of lipid core in the plaque assessed. Cryostat sections were used to quantify the expressions of monocyte/macrophage-2 (MOMA-2), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and matrix metalloproteinases-9 (MMP-9) in the plaque by immunofluorescence method.</p><p><b>RESULTS</b>Blood pressure and lipid profiles were similar among different groups. Compared with control group, the plaque areas of perindopril group and enalapril group displayed significantly decrease (25.33% and 22.86%, respectively, both P < 0.01). However, no significant different were observed in the plaque size between the different ACE inhibitors groups. Perindopril group and enalapril group also significantly decreased the size of lipid core (52.98% and 38.98%, respectively, both P < 0.01) and the expression of MOMA-2 (88.38% and 52.16%, respectively, both P < 0.01), ICAM-1 (80.87% and 49.59%, respectively, both P < 0.01), VCAM-1 (77.56% and 56.44%, respectively, both P < 0.01) and MMP-9 (86.93% and 55.56%, respectively, both P < 0.01), and increased the plaque collagen content (298.36% and 168.14%, respectively, both P < 0.01) and the effects of perindopril was superior to those of enalapril (all P < 0.05).</p><p><b>CONCLUSIONS</b>ACE inhibitors significantly suppressed tissue inflammation and attenuated the development of atherosclerosis in ApoE knockout mice independent of their effects on the lipid and blood pressure. Perindopril is superior to enalapril in stabilizing the plaques and has similar effect on reducing the plaque size as that of enalapril.</p>