PCSK9 induces endothelial cell autophagy by regulating the PI3K/ATK pathway in atherosclerotic coronary heart disease.

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease of the arteries, and its pathogenesis is related to endothelial dysfunction. It has been found that the protein convertase subtilin/kexin9 type (PCSK9) plays an important role in AS, but its specific mechanism is still unclear. METHODS: In this study, we first cultured human umbilical vein endothelial cells (HUVECs) with 50 or 100µg/ml oxidized low-density lipoprotein (ox-LDL) for 24 hours to establish a coronary atherosclerosis cell model. RESULTS: The results showed that ox-LDL induced HUVEC injury and autophagy and upregulated PCSK9 protein expression in HUVECs in a concentration-dependent manner. Silencing PCSK9 expression with siRNA inhibited ox-LDL-induced HUVEC endothelial dysfunction, inhibited the release of inflammatory factors, promoted HUVEC proliferation and inhibited apoptosis. In addition, ox-LDL increased the expression of LC3B-I and LC3B-II and decreased the expression of p62. However, these processes are reversed by sh-PCSK9. In addition, sh-PCSK9 can inhibit PI3K, AKT and mTOR phosphorylation and promote autophagy. CONCLUSION: Taken together, our research shows that silencing PCSK9 inhibits the PI3K/ATK/mTOR pathway to activate ox-LDL-induced autophagy in vascular endothelial cells, alleviating endothelial cell injury and inflammation.

Geo-spatial hotspots of hemorrhagic fever with renal syndrome and genetic characterization of Seoul variants in Beijing, China.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is highly endemic in mainland China, and has extended from rural areas to cities recently. Beijing metropolis is a novel affected region, where the HFRS incidence seems to be diverse from place to place. METHODOLOGY/PRINCIPAL FINDINGS: The spatial scan analysis based on geographical information system (GIS) identified three geo-spatial "hotspots" of HFRS in Beijing when the passive surveillance data from 2004 to 2006 were used. The Relative Risk (RR) of the three "hotspots" was 5.45, 3.57 and 3.30, respectively. The Phylogenetic analysis based on entire coding region sequence of S segment and partial L segment sequence of Seoul virus (SEOV) revealed that the SEOV strains circulating in Beijing could be classified into at least three lineages regardless of their host origins. Two potential recombination events that happened in lineage #1 were detected and supported by comparative phylogenetic analysis. The SEOV strains in different lineages and strains with distinct special amino acid substitutions for N protein were partially associated with different spatial clustered areas of HFRS. CONCLUSION/SIGNIFICANCE: Hotspots of HFRS were found in Beijing, a novel endemic region, where intervention should be enhanced. Our data suggested that the genetic variation and recombination of SEOV strains was related to the high risk areas of HFRS, which merited further investigation.

[Study on the association between hantavirus infection and Rattus norvegicus].

OBJECTIVE: To further understand the association of hantavirus (HV) harbored and transmitted in wild brown rats. METHODS: Rattus norvegicus (n = 570) were trapped in 10 sites in Beijing. RT-PCR was used to test rodent lung samples for hantavirus infection. Unconditional multivariate logistic regression analysis was performed, with PCR positive as the dependent variable and the characteristics of Rattus norvegicus population as independent variables. RESULTS: The overall HV prevalence in Rattus norvegicus was 9.1% (52/570). Significant association between HV infection in Rattus norvegicus and some biological characteristics of host population was observed. Adult Rattus norvegicus had a higher HV prevalence than juveniles. Males in the reproduction periods and rats with wounds were more likely to be infected with HV than others. CONCLUSION: It was further confirmed that there existed parallel transmission of HV in Rattus norvegicus hosts. Aggression might be the primary mode of HV transmission among male Rattus norvegicus.

[Study on the molecular epidemiology of hantaviruse carried by hosts in northern suburb of Beijing].

OBJECTIVE: To investigate hantanvirus infection of captured rodents in Haidian district and Changping district of Beijing and to type hantavirus using molecular technique. METHODS: The captured mice were classified and the density of distribution was calculated. Reverse transcription-polymerase chain reaction (RT-PCR) technique was used to amplify the partial M fragnments of hantaviruse. Several representative positive samples were sequenced and analysed by ClustalX (5.0) and DNAClub software. RESULTS: A total of 414 animals were captured, among which Battus norvegicus was the dominant group. In Haidian district, the median infection rates with hantavirus were 13.14% in Battus norvegicus and 0 in Mus musculus Linnaeus. In Changping district, the average infection rates were 17.46% in Battus norvegicus and 3.57% in Mus musculus Linnaeus. Nucleotide sequences analysis showed that the virus detected all belonged to SEO-type. They clustered with Z37 virus and could be branched into 2 different subclades. CONCLUSION: The major hosts of hantavirus in Haidian and Changping district were Battus norvegicus and the epidemic strains in the two districts of Beijing were genotyped as SEO-type. Nucleotide sequence and deduced amino acid sequence from different rodents were highly homologous, while nucleotide mutation had also been observed. Further studies are required to explore the possible virus sequence mutation.

[Spatial analysis on the distribution of hemorrhagic fever with renal syndrome by geographic information system in Haidian district, Beijing].

OBJECTIVE: To analyze the spatial distribution of hemorrhagic fever with renal syndrome (HFRS) in Haidian district, Beijing and to explore the geographical characteristics of HFRS in highly endemic areas. METHODS: Administration boundary layer was established under the background of 1:100,000 map in the ArcInfo 8.1 software. The HFRS cases from 1997 to 2002 were positioned on the map. Highly endemic areas were identified by spatial cluster analysis using SaTScan 3.0 software. Distribution of HFRS cases was shown in different colors and contours by spatial analysis of geographic information system (GIS). RESULTS: Spatial Cluster Analysis of confirmed cases of HFRS identified in 1997 - 2002 in Haidian district showed that HFRS patients were not randomly distributed. The highly endemic areas were founded in Sujiatuo township, Yongfeng township, Shangzhuang township, Wenquan town and Bei'anhe township (relative risk = 4.43, P = 0.001). A thematic map of HFRS in haidian district was set up. CONCLUSION: HFRS infections were not randomly distributed, since the distribution was related to geographic-environmental factors.

[Epidemiological characteristics of 403 patients with severe acute respiratory syndrome in Haidian district, Beijing].

OBJECTIVE: To analyze epidemiological features of severe acute respiratory syndrome (SARS) in Haidian district, Beijing. METHODS: Each SARS case was interviewed by trained investigator using standardized questionnaire followed a descriptive analysis. RESULTS: Four hundred and three SARS cases were identified and 27 of them died from March 18 and May 31, 2003. The incidence rate of SARS was 18.0/100,000 with case fatality rate as 6.7% in Haidian district, Beijing. Seventy-four percent of patients were adults with higher risk in age group of 20 - 29 year. SARS patients were scattered around in 32 out of 33 streets and villages in this district. The disease appeared to be sporadic but the case of outbreaks in family or university only seen in three streets. The course of SARS epidemic in this district could be divided into three phases: initial-which last for days, peak-21 days and then rapid decline-for 26 days. Number of patients having had a history of close contact to other SARS were gradually decreasing along with the process of the epidemics (trend chi(2) = 8.800, P = 0.003). Seventy-two point seven percent of the SARS cases had been exposed to the injection in the hospital settings. When the epidemics came to a rapid decline, 85.7% of the patients diagnosed during that period could be traced down to have had the history of contacting SARS cases within their own families. The distribution of occupation was also showed significantly different in the three respective stages (chi(2) = 36.41, P < 0.01). Among the patients who could not be identified as having confirmed contact history, 26.6% having had outward activities and 47.6% of them visited hospitals, especially during the peak stage. CONCLUSION: The intensity of SARS epidemic among the residents of Haidian district was recognized as similar to the other parts of Beijing. Nosocomial infection in hospital settings was most important cause responsible for the transmission of SARS in this district.