RESUMO
Coronary events have a close association with a low HDL/hypertriglyceridemia (LHDL/HTG) phenotype. As enzymes that hydrolyze triglyceride-rich lipoproteins are associated with a modulation of both HDL cholesterol and triglycerides, we have tested the hypothesis that mutations in the genes encoding lipoprotein lipase (LPL) or hepatic lipase (HTGL) may contribute to the formation of coronary atherosclerosis and, thus, of coronary heart disease (CHD). The entire coding and boundary regions of LPL and HTGL genes were analyzed by direct sequencing in 20 patients with both LHDL/HTG and diagnosed CHD. In the LPL gene six different polymorphisms were identified with same frequencies observed in the general population. In the HTGL gene, besides several polymorphisms, we identified three missense mutations: Asn37His, Val73Met, and Ser267Phe. Population screening using allele specific PCR identified Val73Met as a polymorphism while the two others were absent from 100 control individuals. One of the mutations (Ser267Phe) is known to cause HTGL deficiency and is associated with type III hyperlipoproteinemia. Since this dyslipoproteinemia meets the criteria of LHDL/HTG, it is intriguing to speculate that missense mutations in HTGL may play a role in the pathogenesis of this atherogenic phenotype.
Assuntos
Doença da Artéria Coronariana/genética , Hiperlipidemias/genética , Lipase/genética , Lipase Lipoproteica/genética , Fígado/enzimologia , Mutação de Sentido Incorreto , Adulto , Idoso , Alelos , Sequência de Bases , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/enzimologia , DNA/análise , Frequência do Gene , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/enzimologia , Lipase/metabolismo , Lipase Lipoproteica/metabolismo , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Valores de Referência , SoftwareRESUMO
For assessing clinical events associated with cardiac allograft vasculopathy, parameters relating to nonimmunological or immunological risk factors, epicardial coronary vessels, microvasculature, or left ventricular function may be utilized.
Assuntos
Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Transplante de Coração/efeitos adversos , Angiografia Coronária , Doença da Artéria Coronariana/mortalidade , Circulação Coronária , Vasos Coronários/diagnóstico por imagem , Endotélio Vascular/fisiopatologia , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Transplante de Coração/imunologia , Humanos , Fluxometria por Laser-Doppler , Masculino , Microcirculação , Prognóstico , Fatores de Risco , Volume Sistólico , Fatores de Tempo , Transplante Homólogo , Ultrassonografia de Intervenção , Função Ventricular Esquerda/fisiologiaRESUMO
Although transplant vasculopathy and native atherosclerosis are clinically and pathologically different entities, the pathogenesis of both diseases exhibits some common mechanisms. Both may be regarded as responses to injury within a broadened concept of the immune system. Alloantigens (e.g. on donor endothelial cells) or autoantigens (e.g. oxydized LDL cholesterol) are presented by antigen presenting cells to the T cells of the body's immune system. With the appropriate costimulatory signal, this signal pattern generates a differentiated T cell, B cell, and inflammatory cell response whereas without the second signal, the immune cells undergo apoptosis. In case of immune cell proliferation and differentiation, a coordinated pattern of cytokine release is initiated. Monocyte-derived macrophages are also involved in this process which culminates in rolling, sticking, and diapedesis through the coronary vascular endothelium and phenotype switch of medial smooth muscle cells mediated by generation of growth-promoting cytokines. Thus, viewed within a broadened paradigm of the immune system's role both disease entities may represent different vignettes of an integrated pathophysiological response to an endothelial injury.
Assuntos
Doença das Coronárias/imunologia , Rejeição de Enxerto/imunologia , Transplante de Coração , Animais , Arteriosclerose/imunologia , Autoantígenos/imunologia , Doença Crônica , Doença das Coronárias/etiologia , Citocinas/imunologia , Citocinas/metabolismo , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Humanos , Isoantígenos/imunologia , Ativação Linfocitária , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Monócitos/imunologia , Óxido Nítrico Sintase/metabolismo , Linfócitos T/imunologia , Transplante Homólogo , Regulação para CimaRESUMO
Rate corrected QT interval (QTc) and QT dispersion (QTd) have been suggested as markers of an increased propensity to arrhythmic events and efficacy of therapy in patients with long QT syndrome (LQTS). To evaluate whether QTc and QTd correlate to genetic status and clinical symptoms in LQTS patients and their relatives, ECGs of 116 genotyped individuals were analyzed. JTc and QTc were longest in symptomatic patients (n = 28). Both QTd and JTd were significantly higher in symptomatic patients than in asymptomatic (n = 29) or unaffected family members (n = 59). The product of QTd/JTd and QTc/JTc was significantly different among all three groups. Both dispersion and product put additional and independent power on identification of mutation carriers when adjusted for sex and age in a logistic regression analysis. Thus, symptomatic patients with LQTS show marked inhomogenity of repolarization in the surface ECG. QT dispersion and QT product might be helpful in finding LQTS mutation carriers and might serve as additional ECG tools to identify asymptomatic LQTS patients.