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Objective@#To evaluate the cardiovascular damage of patients with COVID-19, and determine the correlation of serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (cTnI) with the severity of COVID-19, and the impact of concomitant cardiovascular disease on severity of COVID-19 was also evaluated.@*Methods@#A cross-sectional study was designed on 150 consecutive patients with COVID-19 in the fever clinic of Tongji Hospital in Wuhan from January to February in 2020, including 126 mild cases and 24 cases in critical care. Both univariate and multivariate logistic regression were used to analyze the correlation of past medical history including hypertension, diabetes and coronary heart disease (CHD) , as well as the levels of serum NT-proBNP and cTnI to the disease severity of COVID-19 patients.@*Results@#Age, hypersensitive C-reactive protein(hs-CRP) and serum creatinine levels of the patients were higher in critical care cases than in mild cases(all P<0.05). Prevalence of male, elevated NT-proBNP and cTnI, hypertension and coronary heart disease were significantly higher in critical cases care patients than in the mild cases(all P<0.05). Univariate logistic regression analysis showed that age, male, elevated NT-proBNP, elevated cTnI, elevated hs-CRP, elevated serum creatinine, hypertension, and CHD were significantly correlated with critical disease status(all P<0.05). Multivariate logistic regression analysis showed that elevated cTnI(OR=26.909, 95%CI 4.086-177.226, P=0.001) and CHD (OR=16.609, 95%CI 2.288-120.577, P=0.005) were the independent risk factors of critical disease status.@*Conclusions@#COVID-19 can significantly affect the heart function and lead to myocardial injury. The past medical history of CHD and increased level of cTnI are two independent determinants of clinical disease status in patients with COVID-19.
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Objective To investigate the variation characteristics of peripheral platelet parameters in children with dengue fever and to assess their use and value in diagnosis,prognosis and treatment for dengue fever.Methods Platelet parameters of 69 pediatric patients with dengue fever in acute febrile phase and remission period and 103 healthy controls were compared.The difference of platelet parameters between the liver function injury group and the normal liver function group,the coagulation dysfunction group and the coagulation function normal group,the severe group and the mild group with dengue fever was compared,the causes of thrombocytopenia in children with dengue was investigated so as to better understand the situation of bone marrow producing platelets.Results P-LCR,PDW,MPV were significantly higher in patients in acute febrile phase of dengue fever,compared with the healthy subjects(P＜0.01),while PCT,PLT were significantly lower in patients in acute febrile phase of dengue fever,compared with the healthy subjects(P＜0.01).MPV was significantly lower in patients with abnormal hepatic function when compared with patients with normal hepatic function(P＜0.05),while other platelet parameters did not show significant differences(P＞0.05).PLT and PCT were significantly lower in the severe patients than those in the mild patients(P＜0.05),while other platelet parameters did not show significant differences(P＞0.05).Peripheral platelet parameters did not show significant differences between patients with or without abnormal coagulation function (P＞0.05).Conclusion Peripheral platelet parameters may play a role in the diagnosis,treatment and prognosis of dengue fever in children.
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AIM:Cytochrome P450 epoxygenase 2J2 and epoxyeicosatrienoic acids ( EETs) are known to protect against cardiac hypertrophy and heart failure, which involve activation of 5′-AMP-activated protein kinase ( AMPK) and Akt.Although the functional roles of AMPK and Akt are well established , the significance of crosstalk between them in the development of cardiac hypertrophy and anti -hy-pertrophy of CYP2J2 and EETs remains unclear .Here, we investigated whether CYP 2J2 and its metabolites EETs protected against cardiac hypertrophy by activating AMPKα2 and Akt1.Moreover, we tested whether EETs enhanced crosstalk between AMPKα2 and phosphorylated Akt1 ( p-Akt1), and stimulated the nuclear translocation of p-Akt1, to exert their anti-hypertrophic effects. METHODS:The recombinant rAAV9 vector was coupled to CYP2J2 and the rAAV9-CYP2J2 construct was injected into the caudal vein of AMPKα2-/-and littermate control mice .AMPKα2 -/-and littermate control mice that overexpressed CYP 2J2 in heart were treated with angiotensin II (Ang II) for 2 weeks.Hemodynamic and cardiac functions were also evaluated after 14 days of infusion with Ang II or saline.RESULTS:Interestingly, the overexpression of CYP2J2 suppressed cardiac hypertrophy , including decreased heart size, cross sectional area of cardiomyocytes , markers of cardiac hypertrophy [ brain natriuretic peptide ( BNP) ,β-myosin heavy chain (β-MHC) and skeletal muscle α-actin (ACTA1)] and increased levels of atrial natriuretic peptide (ANP) in the heart tissue and plasma of wild-type mice but not AMPKα2 -/-mice.Measurement of left ventricular ejection fraction and fractional shortening showed that CYP2J2 overexpression prevented Ang II-induced ventricular systolic dysfunction in mice .Moreover, an Ang II-induced reduction in cardiac function, demonstrated by decreased dp/dtmax and dp/dtmin, was prevented by overexpression of CYP2J2.Mechanistically, the CYP2J2 metabolites 11,12-EET activated AMPKα2 to induce the nuclear translocation of p-Akt1, which increased production of ANP and thereby inhibited the development of cardiac hypertrophy .Furthermore , by co-immunoprecipitation analysis , we found that full-length Akt1 and an Akt1 fragment containing amino acids 150-408, which constitute the protein kinase domain , but not other frag-ments of Akt1, bind to the AMPKγ1 subunit.AMPKα2β2γ1 and p-Akt1 interact through the direct binding of the AMPKγ1 subunit to the Akt1 protein kinase domain.This interaction was enhanced by 11,12-EET.CONCLUSION:Our studies reveal a novel mechanism in which CYP2J2 and EETs enhanced Akt1 nuclear translocation through interaction with AMPKα2β2γ1 and protect against cardiac hy-pertrophy and suggest that overexpression of CYP 2J2 might have clinical potential to suppress cardiac hypertrophy and heart failure .
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AIM:Heart failure is characterized by immune activation leading to production and release of proinflammatory cytokines .Inter-leukin 17A (IL-17A) is a proinflammatory cytokine and multiple lines of evidence from animal and human studies suggest crucial roles of IL-17A in heart failure.Therefore, we investigated whether common polymorphisms of genes IL17A and IL17RA (coding interleukin 17 receptor A) gene contribute to genetic predisposition to heart failure and adverse clinical outcomes associated with it .METHODS AND RESULTS:A total of 1713 adults patients with congestive heart failure and 1713 age-and sex-matched controls were genotyped for promoter SNPs, rs2275913 and rs8193037 in IL17A and rs4819554 in IL17RA, to assess the relationship between individual SNPs and the risk of congestive heart failure .Results showed that rs8193037 in IL17A was associated with the risk of congestive heart failure (P<0.01) after adjustment for multiple cardiovascular risk factors including age , sex, smoking status, diabetes, hypertension and dyslipidemia.This association was evident in both ischemic and non-ischemic heart failure (P<0.05).Furthermore, prospective fol-low-up of 12.7 months for the occurrence of adverse clinical outcomes showed that rs 4819554 in IL17RA was significantly associated with cardiovascular mortality (P<0.05) after adjustments for multiple cardiovascular risk factors and New York Heart Association functional class.CONCLUSION:This study demonstrated associations of rs8193037 in the promoter of IL17A with the risk of conges-tive heart failure, and of rs4819554 in the promoter of IL17RA with the risk of cardiovascular mortality in patients with congestive heart failure.These data lend further support to the notion that immune activation and genetic polymorphisms contribute to heart failure path -ogenesis and progression .
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BACKGROUND:Cytochrome P450 ( CYP) epoxygenases metabolize arachidonic acids ( AA) to form epoxyeicosatrienoic acids (EETs), which exert beneficial roles in the treatment of cardiovascular diseases , but little is known about its role on adventitial remo-deling.METHODS:We used C57BL/6J mice in vivo and primary rat adventitial fibroblasts ( AFs) in vitro treated with angiotensin II (Ang II) to investigate the effects of CYP2J2 gene delivery and exogenous EETs administration on adventitial remodeling .RESULTS:CYP/sEH system was found to exist in human adventitia , and involved in adventitial remodeling process .Exogenous EETs administra-tion significantly inhibited Ang II-induced AFs activation , characterized by differentiation , proliferation, migration, and collagen syn-thesis.These protective effects were partially reversed by PPARγantagonist GW9662 pretreatment or SOCS3 siRNA transfection.EETs suppressed Ang II-induced IκBαphosphorylation , subsequent NF-κB nuclear translocation via PPARγdependent signaling pathway in AFs.Additionally, EETs reduced Ang II-induced JAK2, STAT3 phosphorylation and subsequent phosphor-STAT3 nuclear transloca-tion, which were mediated by SOCS3 induction but independent of PPARγactivation.Furthermore, rAAV-CYP2J2 gene delivery re-duced vessel wall thickening , AFs differentiation , proliferation and collagen deposition in aortic adventitia induced by Ang II infusion , which were mediated by NF-κB and SOCS3/JAK/STAT signaling pathways in blood pressure-dependent and -independent manners , re-spectively.CONCLUSION:We concluded that CYP2J2 overexpression attenuated Ang II-induced adventitial remodeling via PPARγ-dependent NF-κB and PPARγ-independent SOCS 3/JAK/STAT inflammatory signaling pathways .
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AIM:The 50-Hz magnetic field (MF) is a potential health-risk factor.Its effects on the cardiovascular system have not been fully investigated .This study was conducted to explore the effects of long-term exposure to 50-Hz MF on the cardiovascular system . METHODS:In the study , an exposure system was constructed and the distribution of 50-Hz MF was detected .Sixty-four Sprague-Dawley (SD) rats were exposed to 50-Hz MF at 100 μT for 24 weeks, 20 hours per day, while another 64 rats were sham exposed. During the exposure, blood pressure was measured every 4 weeks, and 24 weeks later, echocardiography, cardiac catheterisation and electrocardiography were performed .Moreover , heart and body weight were recorded , while haematoxylin-eosin staining and real-time PCR were conducted .RESULTS:The results showed that compared with the sham group , exposure to 50-Hz MF did not exert any effect on blood pressure, pulse rate, heart rate and cardiac rhythm.Further, echocardiography and cardiac catheterisation showed that there were no significant differences in the cardiac morphology and haemodynamics .In addition , histopathological examination showed that 50-Hz MF exposure had no effect on the structure of hearts .Finally, the expression of the cardiac hypertrophic relative genes did not show any significant differences between 50-Hz MF exposure group and the sham group .CONCLUSION: Taken together , in SD rats, exposure to 50-Hz/100-μT MF for 24 weeks did not show any obvious effects on the cardiovascular system .
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AIM:Mitochondrial DNA (mtDNA) copy number variation (CNV), which reflects the oxidant-induced cell damage, has been observed in a wide range of human diseases .However, whether it correlates with heart failure , which is closely related to oxidative stress, has never been elucidated before .We aimed to systematically investigate the association between leukocyte mtDNA CNV and heart failure risk and prognosis .METHODS: A total of 1 700 hospitalized patients with heart failure and 1 700 age-and gender-matched community population were consecutively enrolled in this observational study , as well as 1 638 ( 96.4%) patients were fol-lowed prospectively for a median of 17 months (12~24 months).The relative mtDNA copy number in leukocyte of peripheral blood or cardiac tissue was measured in triplicate by quantitative real-time PCR method .RESULTS:Patients with heart failure possessed much lower relative mtDNA copy number compared with control subjects (P mtDNA copy number depletion is an independent risk factor for heart failure and predicted higher risk of cardiovascular deaths in patients with heart failure .
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Objective To investigate the effects of recombinant adeno-associated virus-mediated myostatin propeptide (MPRO) on uptake and oxidation of glucose,and glycogen synthesis in C2C12 myotubes,as well as the associated molecular mechanism.Methods Mature C2C12 myotubes were assigned to the following 6 groups:control,insulin,green fluorescent protein (GFP),insulin + GFP,MPRO,and insulin + MPRO groups.Glucose uptake,glucose oxidation,and glycogen synthesis were detected by counting radioactivity of 14CO2 or 14C labeled glycogen derived from 2-deoxy-[1-14 C] glucose.The activity of insulin signal pathway was evaluated by Western blot.Results Compared with control group,glucose uptake and glycogen synthesis were significantly increased in insulin and insulin+GFP groups,and further increased in insulin+MPRO group as compared with insulin alone(all P＜ O.05).However,MPRO and insulin had no effect on glucose oxidation.The phosphorylations of insulin receptor (IR) β,insulin receptor substrate 1 (IRS-1),protein kinase B (Akt),glycogen synthase kinase-3 β (GSK-3β),and the expressions of phosphatidylinositol 3-kinase (PI3K) and glucose transporter 4 (Glut4) in membrane were significantly increased in insulin and insulin+GFP groups compared with control group(all P＜0.05),and were further increased after MPRO transfection (all P ＜ 0.05).Conclusion MPRO may increase insulin-stimulated glucose uptake and glycogen synthesis in C2C12 cells by activating the IRS/PI3K/Akt signal pathway.
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This study examined the sodium nitroprusside (SNP) toxicity to central nervous system (CNS) in treatment of patients with aortic dissection (AD). The medical records of 191 AD patients who were admitted to Tongji Hospital, China, from Jan. 1998 to Feb. 2009 were retrospectively analyzed. There were 140 cases of hypertension (73.3%) and 13 cases of Marfan syndrome (6.8%) among the 191 AD patients. A total of 157 patients were given SNP treatment. The toxic reactions of CNS occurred in 18 subjects (11.5%). Most of the adverse reactions occurred on the fifth day following SNP injection. SNP infusion rate was significantly higher in patients who developed CNS toxicity. It was suggested that systemic hypertension is the most common predisposing factor for AD. The combination of SNP with a β-receptor blocker is a medical therapy commonly used in patients with AD. Cyanide and thiocyanate toxicity from SNP treatment is always the consequence of prolonged drug infusion or relatively high dose administration.
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This study examined the sodium nitroprusside (SNP) toxicity to central nervous system (CNS) in treatment of patients with aortic dissection (AD). The medical records of 191 AD patients who were admitted to Tongji Hospital, China, from Jan. 1998 to Feb. 2009 were retrospectively analyzed. There were 140 cases of hypertension (73.3%) and 13 cases of Marfan syndrome (6.8%) among the 191 AD patients. A total of 157 patients were given SNP treatment. The toxic reactions of CNS occurred in 18 subjects (11.5%). Most of the adverse reactions occurred on the fifth day following SNP injection. SNP infusion rate was significantly higher in patients who developed CNS toxicity. It was suggested that systemic hypertension is the most common predisposing factor for AD. The combination of SNP with a β-receptor blocker is a medical therapy commonly used in patients with AD. Cyanide and thiocyanate toxicity from SNP treatment is always the consequence of prolonged drug infusion or relatively high dose administration.
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Aorta , General Surgery , Central Nervous System , Nitroprusside , Therapeutic UsesABSTRACT
This study investigated the effects of telmisartan on insulin resistance in high-fat diet-treated rats and the possible mechanism. A total of 40 male Sprague-Dawley rats enrolled in the study were divided into 4 groups at random: ND group (n=10) and HD group (n=10), in which the rats were given a normal chow diet or a high-fat diet for 20 weeks following a one-week adaptation; ND+telmisartan (n=10) group and HD+telmisartan group (n=10), in which the rats were initially administered in the same way as the ND or HD group, and then they were orally gavaged with telmisartan (5 mg/kg daily) additionally for 5 weeks. Related inflammatory factors were measured by ELISA. Monocyte chemotactic protein 1 (MCP-1), phosphorylated JNK and IκB-α expressions in both adipose and liver were detected by Western blotting. CRP and angiotensin II receptor 1 (AT1) mRNA expressions in both adipose and liver were determined by RT-PCR. The results showed that telmisartan administration in vivo reversed insulin resistance as evidenced by a decrease in plasma fasting glucose levels, plasma fasting insulin levels and homeostasis model of assessment-insulin resistance (HOMA-IR). Furthermore, telmisartan administration significantly reduced serum CRP, TNF-α and IL-1β levels, and elevated serum IL-10 levels. It was also found to hamper the high-fat diet-induced increase in CRP mRNA, AT1 mRNA and MCP-1, and decrease in IκB-α in both adipose and liver. It was concluded that telmisartan administration in vivo may improve insulin resistance through attenuated inflammatory response pathways.
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This study examined the role of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and cystatin C in ischemic stroke complicating atrial fibrillation (AF) and the relationship of systemic inflammation with this disease in order to identify AF patients who are at high risk of stroke and need optimal anticoagulant therapy. A total of 103 AF patients, simple (n=75) or complicated by ischemic stroke (n=28), and 112 control subjects were recruited. IL-6 level was detected by using enzyme linked immunosorbent assay. Cystatin C and hsCRP levels were measured by means of a particle-enhanced immunonephelometric assay. The results showed that the AF patients had higher levels of hsCRP (P=0.004), IL-6 (P=0.000), and cystatin C (P=0.000) than control subjects. Plasma hsCRP level was increased in the AF patients with ischemic stroke as compared to the patients with simple AF (P=0.036). The AF patients who had the level of hsCRP exceeding 3.83 mg/L were at a higher risk than those with hsCRP level lower than 3.83 mg/L (P=0.030). After adjusting for other factors, cystatin C remained positively associated with IL-6 (r=0.613) and hsCRP (r=0.488). It was concluded that hsCRP is positively correlated with ischemic stroke complicating AF and may be a risk factor independent of other risk factors for AF. Elevated cystatin C level is also indicative of the increased risk of AF.
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Increased plasma total homocysteine (tHcy) and high sensitivity C-reactive protein (hsCRP) levels are independent risk factors for cardiovascular disease. However, the predictive value of tHcy in combination with hsCRP in patients with stroke is not known. To determine the relationship between tHcy and hsCRP, we enrolled 291 patients with first-onset stroke (196 ischemic and 95 hemorrhagic). Plasma tHcy and hsCRP levels were measured and subsequent vascular events and deaths were determined over a 5-year period. Using the arbitrary cutoff for tHcy (3 mg/L), the patients were divided into 6 groups. Survival analysis showed that the probability of death or new vascular events during a 5-year follow-up increased according to tHcy and hsCRP levels (P3 mg/L) compared with those with low tHcy (3 mg/L) was still significantly associated with the risk of death or new vascular events (RR, 4.10, 95% CI, 1.61 to 10.45, P=0.003) even when adjusted for other risk factors at inclusion. The combination of increased tHcy and hsCRP levels had a stronger predictive value than increased hsCRP alone or increased tHcy level alone. Further studies are required to evaluate the potential decrease in risks associated with lowering both Hcy and hsCRP levels in patients that present with both increased tHcy and hsCRP.
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Tubulointerstitial fibrosis (TIF) is a common pathological feature of end-stage kidney disease. Previous studies showed that upregulation of TGFbeta1 notably contributed to the chronic renal injury and irbesartan halted the development of TIF in rats with 5/6 renal mass reduction. This study was to investigate the effects of irbesartan on chronic TIF and the mechanism involved TGFbeta1 in the rodent model of chronic renal failure involving 5/6 nephrectomy. The results showed that irbesartan significantly attenuated the rise in blood pressure and tubulointerstitial injury observed in this model. Masson staining of the renal tissue revealed that there appeared severe renal tubule atrophy and fibrosis in operation group, but the lesion was attenuated mostly in irbesartan-treated group. Immunohistochemistry showed that irbesartan treatment apparently decreased the protein expression of TGFbeta1 which was up-regulated in operation groups. Western blot showed that irbesartan treatment down-regulated the expression of TGFbeta1, phosphorylated smad2 (p-smad2), AT1R and phosphorylated p38 (p-p38) MAPK, but significantly up-regulated the protein expression of smad6 as compared with operation group. These findings suggest that irbesartan attenuates hypertension and reduces the development of TIF in rats with 5/6 renal mass reduction via changes in the expression of these proteins at least including smad6, TGF-beta1, p-smad2, AT1 and p-p38 MAPK.
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Objective To analyze relationship between the gene polymorphism of CYP4F2 and essential hypertension (EH) in China's Han population. Methods 189 EH patients and 187 age-matched controls were used to analysis G20597A polymorphism site of CYP4F2 gene with polymerase chain-restriction fragment length polymorphisms. Results There was no difference of neither genotype nor allele of CYP4F2 (G20597A) between EH and controls through stratified analysis on gender. CYP4F2 gene 20597 G allele carriers had significant association with EH for male in China (81.6% vs 71.3% , P =0.019) , but not with female. After adjustment for cardiovascular risk factors (including smoking, TC, age, genetype, BMI) , the hazard ratio for incident EH in male with CYP4F2 20597GG increased about 2. 689 than that with CYP4F2 20597GA and 20597AA. Conclusion CYP4F2 20597G allele has significant association with male EH, and CYP4F2 20597GG may be an independent predictor of EH for male in china's Han population.
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Nitric oxide (NO) is an important signaling molecule with diverse physiological functions in both animal and plant cells. In this work, we isolated the full-length cDNA and genomic DNA sequences of TaNOA-B1 encoding a putative NO associated (NOA) factor in common wheat. Bioinformatic analysis showed that TaNOA-B1 possessed a similar intron/exon structure as its orthologous genes in Arabidopsis and rice. The amino acid sequence deduced from TaNOA-B1 was more than 60% identitical to those of Arabidopsis and rice NOA1 proteins. The primary structure of TaNOA-B1 contained the zinc finger and P-loop GTPase motifs conserved in Arabidopsis and rice NOA1 proteins. There existed at least three NOA gene members in common wheat, which were mapped to homoeologous group six chromosomes 6A, 6B and 6D, respectively. TaNOA-B1 investigated in this work was located on chromosome 6B. The transcripts of TaNOA members were found mainly in leaves. TaNOA-B1-GFP fusion protein may be located in mitochondria. TaNOA transcript level was up-regulated by abscisic acid (ABA) or NaC1 treatments, indicating that TaNOA might be involved in wheat responses to abiotic stresses.
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Amino Acid Sequence , Arabidopsis , Genetics , Cloning, Molecular , DNA, Plant , Genetics , Exons , Genes, Plant , Genetics , Introns , Molecular Sequence Data , Nitric Oxide , Metabolism , Nitric Oxide Synthase , Genetics , Metabolism , Oryza , Genetics , Plant Proteins , Genetics , Metabolism , Triticum , GeneticsABSTRACT
3-hydroxy-3-methylgulutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins are a kind of lipid-lowering agents and have been used for the prevention and treatment of cardiovascular diseases. Recent studies suggested that statins, besides lowering cholesterol, may protect vessels by enhancing the activity of endothelial nitric oxide synthase (eNOS). In the present study, we investigated if simvastatin increases eNOS activity through its phosphorylation in 293 cells (293-eNOS) with stable expression of eNOS. The results showed that incubation of 293-eNOS cells with simvastatin (10 microm/L) for 2 h significantly increased in the activity of eNOS as shown by the conversion of L-arginine to L-citrulline (2889.70+/-201.51 versus 5630.18+/-218.75 pmol/min . mg proteins) (P<0.01). Western blotting revealed that simvastatin increased phosphorylation of eNOS at 1177 (ser) and also 495 (thr) but did not affect the overall expression of eNOS or inducible NOS. Further study found that simvastatin raised phosphorylation levels of Akt and AMPK, and such effect could be antagonized by Akt inhibitor or AMPK inhibitor. These results suggest that simvastatin could stimulate the activity of eNOS via its phosphorylation by Akt and AMPK, which provides a new mechanism, other than lipid-lowering effect, for the cardiovascular protection of statins.
Subject(s)
Cell Line , Epithelial Cells/cytology , Epithelial Cells/enzymology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Kidney/cytology , Nitric Oxide Synthase Type III/metabolism , Phosphorylation , Simvastatin/pharmacologyABSTRACT
sfection could promote the expression of integrin α3β1/α6β1. The mechanism of regulating integrin α3β1/α6β1 may lie in allosterism of an extracellullar CDI51 site (QRD194-196) and C -terminal Ves. transportation target motif(YRSL245-248).
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Objective To investigate the effect of CD151 gene therapy on improving myocardial function in swines with myocardial infarction. Methods CD151, antisense CD151 and green fluorescent protein (GFP) were constructed into the recombinant adeno-associated virus (rAAV). Swines were divided into 4 groups: rAAV-GFP group (6 swines), rAAV-CD151 group (6 swines), rAAV-antiCD151 group (6 swines) and control group (6 swines). The swines were performed with coronary artery ligation and intramuscularly injection with rAAV. Eight weeks after vector administration, western blot was used to detect gene expression of CD151. 13N-labeled NH3 positron emission tomography (PET) was used to evaluate myocardial perfusion. Echocardiography was used to assess myocardial function. Results Compared with the control group and the rAAV-GFP group, the rAAV-CD151 group showed higher CD151 protein expression. Compared with the rAAV-GFP group, the defect size of myocardium was decreased[( 11.3±2.4)% vs. (21.1±2.6)%, t= -5.67,P<0.01] and left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), the ratio of anterior lateral wall thickening (△ALWT) and ratio of interventricular septum thickening (△IVST) were significantly improved in rAAV-CD151 group 8 weeks after vector administration [(65.7±4.6)% vs. (54.7±5.3)%, (36.0±2.9)% vs. (27.6±3.1)%,(55.4± 4.9)% vs. (36.8±7.8)%, (35.2±6.0)% vs. (26.7±4.4)%, t=3.98, 3.35, 3.34, 9.27, all P< 0.05]. The level of diastolic ALWT and diastolic IVST was also increased in rAAV CD151 group compared with rAAV-GFP group ( P<0.05).Compared with rAAV-CD151 group, parameters of myocardial function in rAAV-antisense CD151 group were not improved (P<0.05). Conclusions rAAV-CD151 can effectively transfeet the myocardium, increase the expression ofCD151 protein, promote the blood perfusion of myocardium and improve the ventricular function after myocardial infarction.
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Objective To evaluate the delivery of recombinant adeno-associated virus(rAAV)-mediated CD151 gene in promoting neovascularization and coronary collateralization in swines after myocardial infarction.Method Twenty-six chinese minipigs(clean,provided by breeding pig farm of Huazhong Agricultural University) were randomly divided into four groups:(1)normal control group(n=4):swines without surgery.(2)rAAV-GFP group(n=7):The acute myocardial infarction models were produced in swines by ligating the left anterior descending coronary artery(LAD).The success criteria of the models was that ST-segment elevations in leatds I and aVL maintained for 20 minutes.The rAAV-GFP was injected into the left ventricular anterior wall(divided into 10 points,1×10 11 pfu/point).(3)rAAV-CD151 group(n=7):The operation method was the same as rAAV-GFP group.The rAAV-CD151 was injected into the left ventrieular anterior wall(divided into 10 points).(4) rAAV-antiCD151 group(n=8):The operation method was the same as rAAV-GFP group.The rAAV-antiCD151 was injected into the left ventricular anterior wall(divided into 10 points).Eight weeks after coronary artery liga-tion,the expression of CD151 was measured by western blot.Coronary angiography was done to evaluate collateral circulation of the infarct zone of myocardium.The infurct size was determined by staining with triphenyl-tetrazolium chloride(TTC).Statistical analysis wan carried out by using one-way analysis of variances.Results High level of CD151 protein expression was detected.Coronary angiography showed better collateral circulation in the rAAV-CD151 group.The percentage of infarct size was sinificanly lower in the rAAV-CD151 group (12.82±2.26)% than that in the other two groups,and that was higber in rAAV-anti-CD151 group(32.52±3.47)% than that in the rAAV-GFP group(23.14%±2.83%,both P＜0.05).Conelusions CD151 in vivo gene transferred to swines with acute myocardial infarction promotes neovascularization and thereby improves collateral circulation.