Jianyan Wen

Adiponectin protects against cerebral ischemia-reperfusion injury through anti-inflammatory action.

Adiponectin (APN), a circulating adipose-derived hormone regulating inflammation and energy metabolism, has beneficial actions on cardio- and cerebrovascular disorders. Hypoadiponectinemia is associated with ischemic cerebrovascular disease, however, little is known about the cerebroprotective action of APN as well as its molecular mechanisms. In the present study, the role of APN in the pathogenesis of acute cerebral injury was investigated. Rats were divided into three groups: (i) a sham operation group; (ii) an ischemia/reperfusion (I/R) group, rats were subjected to 1 h middle cerebral artery occlusion followed by 23 h reperfusion (I/R); (iii) a APN-treated group, two bolus of 5 microg APN was administered through jugular vein before and after operation. I/R resulted in obvious cerebral infarct size, neurological deficits, and increased expression of endogenous immunoglobin G and matrix metalloproteinase 9, which can be significantly diminished by administration of APN. We also found that APN can significantly inhibited cerebral expression of myeloperoxidase, a distinct indicator of inflammatory cell infiltration, and inflammatory cytokines, interleukin (IL)-1beta, tumor necrosis factor-alpha and IL-8 in response to I/R, suggesting that APN exerts potent anti-inflammatory actions. Furthermore, nuclear factor (NF)-kappaB (p65), a critical transcription factor involved in inflammatory reactions, was observed predominantly located in the nucleus after I/R, whereas APN can obviously inhibit its translocation from cytoplasm into the nucleus. Results of this study demonstrate that APN exerts a potent cerebroprotective function through its anti-inflammatory action, and NF-kappaB (p65) is a key component in this process. APN might be potential molecular targets for ischemic stroke therapy.

Adiponectin induces interleukin-6 production and activates STAT3 in adult mouse cardiac fibroblasts

Background information. APN (adiponectin), an adipocyte‐derived cytokine highly presented in serum, which exerts antidiabetic, anti‐atherosclerotic and cardioprotective actions, also enhances CFB (cardiac fibroblast) proliferation and protects against cardiac fibrosis. STAT3 (signal transducer and activator of transcription 3), a major mediator in the gp130/JAK2 (Janus kinase 2)/STATs signalling pathway, plays a critical role in cardioprotective events. Almost two‐thirds of total myocardial cells are CFBs; however, whether APN regulates STAT3 signalling pathway has not been clarified yet in CFBs. In the present study, we investigated the effect of recombinant globular APN on the STAT3 activity in adult mouse CFBs and explored the possible signalling transduction mechanism.

Rosiglitazone promotes atherosclerotic plaque stability in fat-fed ApoE-knockout mice.

Type 2 diabetes is considered a risk equivalent for cardiovascular disease, rosiglitazone, as an insulin sensitizer, has been explored as a novel therapeutic drug for the prevention of cardiovascular disease, but whether it can stabilize vulnerable atherosclerotic plaques is still unknown. Our study aims to investigate the effect of rosiglitazone on plaque stability in fat-fed ApoE-knockout mice. Our findings showed that rosiglitazone can stabilize the vulnerable atherosclerotic plaques in fat-fed ApoE-knockout mice by modifying the plaque composition as well as decreasing the number of buried fibrous caps and its anti-inflammatory effect probably is the key mechanism through which promotes the plaque more stable.

NOVEL MITOCHONDRIAL DNA MUTATIONS ASSOCIATED WITH CHINESE FAMILIAL HYPERTROPHIC CARDIOMYOPATHY

1 Hypertrophic cardiomyopathy (HCM) is a genetic disorder that has a complex set of symptoms and potentially devastating consequences. Increasing evidence indicates that mitochondrial DNA (mtDNA) mutations are responsible for the development of HCM, but the mtDNA mutations appear to differ considerably among different populations and regions. 2 In the present study, three families with HCM were found and investigated: one in Shandong province and two in the Chongqing region of China. The entire mtDNA genome from the 18 affected and 66 unaffected family members was sequenced directly and the mtDNA mutations were determined. 3 The frequency of haplogroup M10 was significantly higher in family members with HCM (HCM group) than in unaffected family members (normal group). Three mtDNA mutations were found with a significantly higher frequency in affected individuals than in unaffected family individuals, namely G7697A in the cytochrome c oxidase subunit II gene (P < 0.0001; odds ratio (OR) 227.5; 95% confidence interval (CI) 23.6–2194.8) and T12477C (P = 0.0037; OR 5.6; 95% CI 1.8–17.6) and G13135A in the NADH dehydrogenase 5 gene (P < 0.0001; OR 26.0; 95% CI 6.9–98.3), suggesting that these mutations are probably associated with susceptibility to HCM. In addition, mitochondrial Complex I activity was markedly decreased in the HCM group, suggesting that these mutations most likely affect mitochondrial respiratory function. 4 In conclusion, the results of the present study imply that mtDNA mutations G7697A, T12477C and G13135A are genetic factors that indicate a susceptibility to HCM and that could be used for the large‐scale screening of genetic markers as well as the early diagnosis of HCM.

ITIH4: A New Potential Biomarker of ''Toxin Syndrome'' in Coronary Heart Disease Patient Identified with Proteomic Method

Objective. This trial aims to look for the protein biomarker of “toxin syndrome” of CHD patients. Methods. We have performed two trials in this paper. The first trial was a randomized controlled trial (RCT) of the plasma proteome in unstable angina (UA) patients by Maldi-Tof Mass. The second trial was a nested case-control study in 1503 stable CHD patients with one-year followup for acute cardiovascular events (ACEs). Results. In the RCT study, 12 protein spots were found to be the differential protein for the significant differences between the difference of before and after treatment in group A and group B; 2 of them (3207.37u2009Da and 4279.95u2009Da) was considered to be unique to “toxin syndrome” for being differential proteins of group B but not group A. These 2 spots were identified as Isoform 1 of Fibrinogen alpha chain precursor (FGA, 3207.37u2009Da) and Isoform 2 of inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4, 4279.95u2009Da), respectively. In the nested case-control study, the result of Western blot demonstrated that protein expression of ITIH4 in the group with followup ACEs was significantly lower than the matched group without followup ACEs (P = 0.027). Conclusion. ITIH4 might be a new potential biomarker of CHD “toxin syndrome” in TCM, indicating the potential role in early identifying high-risk CHD patients in stable period.

A Preliminary Study of the Therapeutic Role of Human Early Fetal Aorta-derived Endothelial Progenitor Cells in Inhibiting Carotid Artery Neointimal Hyperplasia

Background: 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. Methods: 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. Results: 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. Conclusion: EPCs derived from human early fetal aorta were successfully transplanted into injured vessels and might inhibit neointimal hyperplasia after vascular injury.

Exosomes of Endothelial Progenitor Cells Inhibit Neointima Formation After Carotid Artery Injury

BACKGROUNDnExosomes released from endothelial progenitor cells (EPCs) play a protective role in various disease models. Both endothelial cell (EC) damage and smooth muscle cell (SMC) proliferation are involved in the pathological process of restenosis after angioplasty and stenting. Few studies have focused on the therapeutic role of exosomes in EC damage and SMC proliferation. In this study, we sought to investigate the effect of exosomes released by human fetal aorta-derived EPCs on the rat carotid artery balloon injury model inxa0vivo. We also sought to determine the effect of exosomes on both ECs and SMCs inxa0vitro.nnnMETHODSnExosomes (Exo group) or saline (Con group) were injected in rat carotid balloon injury model animals. The rats were sacrificed after 2, 4, 14, and 28 d, and injured carotid specimens were collected for Evans blue staining, hematoxylin-eosin staining, and immunohistochemistry.nnnRESULTSnWhen the Con group and the Exo group were compared, the reendothelialized areas were not significantly different after 2 or 4 d, as shown by Evans blue staining. The hematoxylin-eosin results showed that the intimal to medial area ratio was slightly but not significantly higher in the Exo group after 2 and 4 d. The immunohistochemistry results showed that the proliferation of SMCs was slightly higher in the Exo group after 2 and 4 d, but the difference was not significant. The reendothelialization area of the Con group was significantly smaller than that of the Exo group at day 14. Both the intimal to medial area ratio and SMC proliferation in the Exo group were significantly smaller than those of the Con group at 14 or 28 d. In the inxa0vitro study, exosome treatment significantly enhanced the proliferation and migration of both ECs and SMCs.nnnCONCLUSIONSnExosomes derived from EPCs could inhibit neointimal hyperplasia after carotid artery injury in rats. The protective effect of exosomes may manifest through the promotion of EC repair rather than direct suppression of proliferation and migration of smooth muscles cells.

Surgical treatment of recurrent varicose veins in the lower limbs associated with endovascular treatment of iliac vein stenosis

OBJECTIVEnWe present our experience with endovascular surgery for recurrent varicose veins (RVV) of the lower limbs combined with the iliac vein compression syndrome (IVCS).nnnMATERIALS AND METHODSnThis study was a retrospective analysis of 6 patients with RVVs combined with IVCS who were admitted to our hospital between January 2007 and December 2014. Transfemoral venography was performed to confirm IVCS. Balloon dilation and stent placement were successful in all 6 patients. The varicose veins were treated by traditional surgery after the endovascular therapy. The visual analog pain scale (VAS) score and venous clinical severity score (VCSS) were collected before surgery and at 6-months follow-up, and were analyzed using the paired student t-test. Patency of the iliac vein was assessed via duplex Doppler ultrasound.nnnRESULTSnThe rate of technical success was 100%. There was a significant (pu202f<u202f.001) improvement in VCSS postoperatively. During the 6-month follow-up period, no RVVs were observed and the rate of iliac vein patency was 100%. Importantly, VAS ratings also decreased significantly (pu202f<u202f.001) during the follow-up.nnnCONCLUSIONnEndovascular surgery for IVCS combined with traditional surgery focused on varicose veins is an effective procedure for treating RVVs of the lower limbs associated with IVCS within 6 months.

Is Human-induced Pluripotent Stem Cell the Best Optimal?

Objective: 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. Data Sources: Articles in this review were searched from PubMed database from January 2014 to December 2017. Study Selection: Original articles about iPSCs and cardiovascular diseases were included and analyzed. Results: 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. Conclusions: 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.