Assuntos
Aterosclerose/virologia , Betacoronavirus , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Trombose/virologia , Doença Aguda , Aterosclerose/fisiopatologia , COVID-19 , Infecções por Coronavirus/fisiopatologia , Humanos , Pneumonia Viral/fisiopatologia , Prognóstico , SARS-CoV-2 , Trombose/fisiopatologiaAssuntos
Humanos , Pneumonia Viral/complicações , Trombose/virologia , Infecções por Coronavirus/complicações , Aterosclerose/virologia , Pandemias , Betacoronavirus , Pneumonia Viral/fisiopatologia , Prognóstico , Trombose/fisiopatologia , Doença Aguda , Infecções por Coronavirus , Infecções por Coronavirus/fisiopatologia , Aterosclerose/fisiopatologiaRESUMO
The objective of this study was to observe the infection of human cytomegalovirus (HCMV) to human umbilical vein endothelial cells, and its effect on the expression of single-stranded DNA-binding protein (SSBP1) and on lipid metabolism in endothelial cells. We screened the differential expression of mRNAs after HCMV infection by suppression subtractive hybridization and the expression levels of SSBP1 mRNA and protein after HCMV infection by real-time PCR and western blot. After verification of successful infection by indirect immunofluorescent staining and RT-PCR, we found a differential expression of lipid metabolism-related genes including LDLR, SCARB, CETP, HMGCR, ApoB and LPL induced by HCMV infection. The expression levels of SSBP1 mRNA and protein after HCMV infection were significantly down-regulated. Furthermore, we found that upregulation of SSBP1 inhibited the expression of atherosclerosis-associated LDLR, SCARB, HMGCR, CETP as well as the accumulation of lipids in the cells. The results showed that the inhibition of SSBP1 by HCMV infection promotes lipid accumulation in the cells.
Assuntos
Infecções por Citomegalovirus/metabolismo , Proteínas de Ligação a DNA/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/virologia , Metabolismo dos Lipídeos/fisiologia , Proteínas Mitocondriais/metabolismo , Aterosclerose/metabolismo , Aterosclerose/virologia , Colesterol/análise , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Proteínas de Ligação a DNA/genética , Regulação para Baixo , Humanos , Hidroximetilglutaril-CoA Redutases/metabolismo , Metabolismo dos Lipídeos/genética , Proteínas Mitocondriais/genética , Receptores de LDL/metabolismo , Receptores Depuradores Classe B/metabolismo , Fatores de TempoRESUMO
The objective of this study was to observe the infection of human cytomegalovirus (HCMV) to human umbilical vein endothelial cells, and its effect on the expression of single-stranded DNA-binding protein (SSBP1) and on lipid metabolism in endothelial cells. We screened the differential expression of mRNAs after HCMV infection by suppression subtractive hybridization and the expression levels of SSBP1 mRNA and protein after HCMV infection by real-time PCR and western blot. After verification of successful infection by indirect immunofluorescent staining and RT-PCR, we found a differential expression of lipid metabolism-related genes including LDLR, SCARB, CETP, HMGCR, ApoB and LPL induced by HCMV infection. The expression levels of SSBP1 mRNA and protein after HCMV infection were significantly down-regulated. Furthermore, we found that upregulation of SSBP1 inhibited the expression of atherosclerosis-associated LDLR, SCARB, HMGCR, CETP as well as the accumulation of lipids in the cells. The results showed that the inhibition of SSBP1 by HCMV infection promotes lipid accumulation in the cells.
Assuntos
Humanos , Infecções por Citomegalovirus/metabolismo , Proteínas de Ligação a DNA/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/virologia , Metabolismo dos Lipídeos/fisiologia , Proteínas Mitocondriais/metabolismo , Aterosclerose/metabolismo , Aterosclerose/virologia , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Colesterol/análise , Proteínas de Ligação a DNA/genética , Regulação para Baixo , Hidroximetilglutaril-CoA Redutases/metabolismo , Metabolismo dos Lipídeos/genética , Proteínas Mitocondriais/genética , Receptores de LDL/metabolismo , Receptores Depuradores Classe B/metabolismo , Fatores de TempoRESUMO
BACKGROUND: Cardiovascular diseases (CVD) are a major cause of death in people with AIDS. Factors contributing to atherosclerosis include traditional risk factors, antiretrovirals and inflammatory factors related to HIV infection. This study set out to compare risk factors associated with subclinical atherosclerosis in individuals under and over 40 years of age. METHODS: Case-control study with 697 HIV/AIDS individuals without HAART or who remain on their first antiretroviral regimen. Of the total, 351 individuals under 40 years and 346 over 40 years were analyzed separately. Subclinical atherosclerosis was assessed by carotid intima-media thickness, using B-mode ultrasound. Multivariate logistic regression was performed to find predictors of subclinical atherosclerosis in the entire group. Subsequent analysis excluded patients with major risk factors for CVD. Magnitudes of associations were expressed by odds ratio (OR) statistical significance, using a 95% confidence interval and p-value <0.05. RESULTS: In the <40 years group subclinical atherosclerosis was associated with male gender (OR: 2.77, 95% CI: 1.43-5.34), nonwhite race (OR: 3.01, 95% CI: 1.23-6.53), obesity (OR: 5.13, 95% CI: 1.79-14.7) and metabolic syndrome (OR: 3.30, 95% CI: 1.44-7.58). In the group ≥40 years predictors of subclinical atherosclerosis were overweight and obesity (OR = 2.53, 95% CI, 0.85-7.54), current CD4 ≥350 cells/mL (OR: 2.81, 95% CI: 1.22-6.47) and NNRTI use ≥ 5 years (OR: 2.65, 95% CI: 1.10-6.37) or PI use >5 years (OR: 1.81, 95% CI: 0.38-8.59). In the multivariate model excluding patients with major risk factors for CVD, age, male sex and nonwhite race were associated with subclinical atherosclerosis in the <40 y group, while in the ≥40 y group, age, HIV viral load >10,000 copies and the use of NNRTI (OR: 7.60, 95% CI: 1.61-35.8) or PI ≥5 years (OR: 3.62, 95% CI: 0.48-26.8) were associated with subclinical atherosclerosis. CONCLUSIONS: In young people the fight against obesity and metabolic syndrome is the main aim in the prevention of CVD. In individuals aged ≥40 y, the prevention of obesity is also of great importance. Moreover, the effects of uncontrolled viremia and the prolonged use of HAART appear to be more harmful in the older group.
Assuntos
Aterosclerose/virologia , Infecções por HIV/patologia , Adulto , Análise de Variância , Doenças Assintomáticas , Aterosclerose/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Feminino , Infecções por HIV/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores SocioeconômicosRESUMO
BACKGROUND: Antibodies against low-density lipoproteins (LDLs) that have been oxidized are associated with development of atherosclerotic lesions. In individuals infected with human immunodeficiency virus type 1 (HIV-1) with or without therapy, dyslipidemia and increased cardiovascular risk are observed. METHODS: Serum levels of IgG antibodies against oxidized LDLs (IgG anti-oxLDL Abs) were determined by assay in 151 HIV-1-infected patients. Of these, 42 patients did not receive anti-retroviral therapy (ART-naïve), whereas 109 received highly active anti-retroviral therapy (HAART) consisting of lopinavir/ritonavir (LOP/r; n=50), efavirenz (EFV; n=30) and nevirapine (NVP; n=29) associated with nucleoside reverse transcriptase inhibitors. HIV-1 seronegative individuals (n=43) participated in the study. The following parameters were quantified: total cholesterol and its fractions, atherogenic indices (AIs), apolipoproteins A1 and B100, high sensitivity C-reactive protein, CD4+ and CD8+ T cells, and HIV-1-RNA. RESULTS: Levels of IgG anti-oxLDL Abs were significantly higher (p<0.05) in the LOP/r group compared with the EFV and/or NVP and the seronegative group: median 0.32 (0.15, 0.58; 95% confidence interval) vs. 0.25 (0.13, 0.53) vs. 0.18 (0.04, 0.38), respectively. HIV-1-infected ART-naïve patients (n=42) presented antibodies levels similar to those observed for the LOP/r group, 0.33 (0.13, 0.63; p>0.05). The levels of IgG anti-oxLDL Abs correlated with an increase in AIs (r=0.216; p=0.036) and triglycerides (r=0.220; p=0.044) in the LOP/r group, and AIs in the ART-naïve group (r=0.300; p=0.046). CONCLUSIONS: Patients treated with LOP/r showed higher levels of IgG anti-oxLDL Abs compared with patients treated with EFV or NVP regimens, and these levels were associated with an increase in AIs.
Assuntos
Aterosclerose/sangue , Dislipidemias/sangue , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Imunoglobulina G/sangue , Lipoproteínas LDL/imunologia , Inibidores de Proteases/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Aterosclerose/imunologia , Aterosclerose/virologia , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
Cardiovascular diseases account for 20% of deaths worldwide, rising to 50% in developed countries. Current understanding of atherosclerosis derives from a combination of research in animals and cell cultures, analysis of human lesions, clinical investigations of patients with acute coronary syndromes and epidemiological studies of coronary artery disease. By measuring serologic titers in the serum of patients after cardiovascular events, it was observed that the greater the infectious exposure of a patient, the larger the atherosclerotic lesion extension. In addition, gene targeting or pharmacological inhibition of certain cytokines aggravates atherosclerosis in animal experiments. Other animal experiments have succeeded in proving that B cells play a protective role in atherosclerosis through induced immunity against oxidized low-density lipoprotein and other epitopes. Molecular mimicry might respond to the question of how infection may trigger vulnerability in previously stable atherosclerotic lesions. The FLU Vaccination Acute Coronary Syndromes trial enhanced the debate on atherosclerosis prevention by the application of antiflu vaccine. So far, antibiotics have failed to reduce cardiovascular risk, as recent trials could not demonstrate a statistically significant risk reduction. Having assumed atherosclerosis to be an inflammatory disease, the WHO considered the possible role of secondary prevention with antiflu vaccine.