RESUMO
Introdução: Pacientes soropositivos tratados com antirretrovirais(ARV) apresentam alterações do perfil lipídico. Polimorfismos dasapolipoproteínas A5 (-1131T/C) e E estão associados à dislipidemia,ocasionando aumento dos triglicerídios e resistência aos hipolipemiantes.Objetivo: Avaliar os efeitos da infecção pelo vírus da imunodeficiência humana (VIH) e dos polimorfismos das apos A5 e E sobre o perfil lipídico em pacientes ambulatoriais infectados, pré e pós-uso de ARV. Método: Estudo de coorte, observacional, prospectivo, analítico, com grupo controle, realizado entre agosto de 2008 e dezembro de 2011. Incluídos, do diagnóstico de VIH aos dias atuais, 89 pacientes de ambos os sexos, faixa etária entre 12 anos e 68 anos,sob uso ou não de terapia antirretroviral altamente ativa (HAART),atendidos no ambulatório de Cardiologia Preventiva-VIH do Hospital Universitário Antônio Pedro (Huap), UFF. Resultados: Dentre os parâmetros bioquímicos, a elevação dos triglicerídios relacionada à infecção pelo VIH e à HAART foi a mais evidente durante o estudo. Considerando o polimorfismo da apoA5, 22,4% (n = 20) dos pacientes analisados apresentaram o alelo C no seu genótipo, em comparação com 4,5% (n = 9) do grupo controle de soronegativos. Não houve diferenças significativas entre os perfis metabólicos de VIH+ que continham ou não o alelo C. Conclusão: Não houve diferença entre VIH+ carreadores do alelo C em relação àqueles não carreadoresquanto à necessidade de substituir a HAART devido à dislipidemia resistente aos hipolipemiantes. Os papéis inflamatório e aterogênico da infecção pelo VIH sobrepõem-se ou têm efeito maior do que o polimorfismo -1131T/C da apoA5 no desenvolvimento de distúrbios metabólicos.
Introduction: HIV - positive patients treated with antiretroviral(ARV) drugs have changes on lipid profile. Apolipoproteins A5(-1131TC) and E polymorphisms are associated with dyslipidemia,causing increased triglycerides and resistance to lipid-lowering drugs.Objective: Evaluate the effects of human immunodeficiency virus(HIV) infection and apoA5 and apoE polymorphisms on the lipid profileof infected outpatients, pre and post-use of ARV. Method: Cohort,observational, prospective, analytical study, with control group,between August 2008 and December 2011. Since the HIV diagnosisto the present day, 89 patients of both sexes were included, agedbetween 12 years and 68 years, under use or nonuse of highly activeantiretroviral therapy (HAART), all of them attended at PreventiveCardiology Clinic-HIV Antônio Pedro University Hospital (Huap),UFF. Results: Among the biochemical parameters, the elevation oftriglycerides related to HIV infection and to HAART was the most evidentduring the study. Considering the apoA5 polymorphism, 22.4% (n= 20) of the patients examined presented the C allele in their genotype,compared to 4.5% (n = 9) of the seronegative control group. Therewere no significant differences between the HIV metabolic profilesthat contained the C allele or not. Conclusion: There was no differencebetween HIV+ C allele carriers in relation to non-carriers on the needto replace the HAART due to lipid-lowering resistance dyslipidemia.The inflammatory and atherogenic roles of HIV infection overlap orhave greater effect than the ApoA5 -1131T/C polymorphism in thedevelopment of metabolic disorders.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Apolipoproteínas A/efeitos adversos , HIV , Soropositividade para HIV/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Estudos Transversais/métodos , Fatores de Risco , Transtornos do Metabolismo dos Lipídeos/induzido quimicamenteRESUMO
Many proteins in the fibrinolysis pathway contain antiangiogenic kringle domains. Owing to the high degree of homology between kringle domains, there has been a safety concern that antiangiogenic kringles could interact with common kringle proteins during fibrinolysis leading to adverse effects in vivo. To address this issue, we investigated the effects of several antiangiogenic kringle proteins including angiostatin, apolipoprotein(a) kringles IV(9)-IV(10)-V (LK68), apolipoprotein(a) kringle V (rhLK8) and a derivative of rhLK8 mutated to produce a functional lysine-binding site (Lys-rhLK8) on the entire fibrinolytic process in vitro and analyzed the role of lysine binding. Angiostatin, LK68 and Lys-rhLK8 increased clot lysis time in a dose-dependent manner, inhibited tissue-type plasminogen activator-mediated plasminogen activation on a thrombin-modified fibrinogen (TMF) surface, showed binding to TMF and significantly decreased the amount of plasminogen bound to TMF. The inhibition of fibrinolysis by these proteins appears to be dependent on their functional lysine-binding sites. However, rhLK8 had no effect on these processes owing to an inability to bind lysine. Collectively, these results indicate that antiangiogenic kringles without lysine binding sites might be safer with respect to physiological fibrinolysis than lysine-binding antiangiogenic kringles. However, the clinical significance of these findings will require further validation in vivo.
Assuntos
Apolipoproteínas A/química , Apolipoproteínas A/farmacologia , Fibrinólise/efeitos dos fármacos , Kringles , Lisina , Plasminogênio/química , Plasminogênio/farmacologia , Sequência de Aminoácidos , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/química , Inibidores da Angiogênese/metabolismo , Inibidores da Angiogênese/farmacologia , Angiostatinas/efeitos adversos , Angiostatinas/química , Angiostatinas/metabolismo , Angiostatinas/farmacologia , Apolipoproteínas A/efeitos adversos , Apolipoproteínas A/metabolismo , Sítios de Ligação , Relação Dose-Resposta a Droga , Fibrina/metabolismo , Fibrinogênio/química , Fibrinogênio/metabolismo , Humanos , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Plasminogênio/efeitos adversos , Plasminogênio/metabolismo , Trombina/química , Trombina/metabolismo , Ativador de Plasminogênio Tecidual/metabolismoRESUMO
BACKGROUND: Studies have reported an increase in median Lipoprotein (Lp) (a) in patients with high molecular weight (HMW) apolipoprotein (apo) (a) isoforms and renal impairment. Some studies identify Lp (a) levels as a risk factor for vascular disease in renal failure whilst others have demonstrated an association with apo (a) isoform type and vascular disease. METHODS: A total of 239 patients at end-stage renal failure (ESRF) were studied prior to the initiation of dialysis. Blood was taken for Lp (a) levels and apo (a) isoforms. Clinical vascular disease (CVD) was assessed on the basis of clinical history and Rose questionnaire. The control group for Lp (a) levels consisted of 228 healthy volunteers. RESULTS: Despite a higher median Lp (a) level in those with HMW isoforms, 30% of patients had Lp (a) levels <10 mg/dl. Overall, 49% patients were identified as having CVD. Diabetes, smoking history and Lp (a) levels were significantly associated with CVD in logistic regression analysis, although when patients with low molecular weight (LMW) and HMW isoforms were analysed separately, Lp (a) levels were not significantly associated with CVD in those with LMW isoforms. The rates of CVD in those with HMW isoform and low Lp (a) levels were significantly lower than those with HMW isoforms and elevated Lp (a) levels, 34 vs 57% (P < 0.01). CONCLUSIONS: Although median Lp (a) levels in those patients at ESRF with HMW isoforms are higher than controls, in a third of such patients Lp (a) levels remain relatively low. These patients have lower rates of CVD than those with high levels of Lp (a).
