Lewis William
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
AIDS. 2003 Apr;17 Suppl 1:S36-45. doi: 10.1097/00002030-200304001-00006.
Heart disease in AIDS, particularly cardiomyopathy (CM), is an increasingly recognized clinical problem with as yet undefined pathogenetic mechanisms. Among the potential etiologies of AIDS CM are HIV-1 infection of cardiac myocytes and subsequent cardiac dysfunction, opportunistic infection, inflammatory reactions, cytokine effects, and cardiotoxicity of prescribed or illicit drugs. It seems probable that multiple factors may impact on the development of CM in AIDS. Transgenic mice (TG) are useful biological tools to explore mechanisms of cardiac function and disease. In AIDS models, TG offer novel ways to elucidate mechanisms of AIDS CM through combined in vivo and in vitro studies. With targeted and non-targeted TG, structural and functional effects of specific HIV-1 gene products on heart tissue may be addressed. The impact of environmental agents including therapeutics or cardiotoxins may also be defined. To address the complexity of AIDS CM using TG, an experimental approach has been employed in our laboratories to model the clinical condition. We utilize AIDS TG with generalized expression of HIV-1 gene products in CM models with combined antiretroviral regimens to define the cardiovascular effects of AIDS and its therapy on the structure and function of the murine heart. We are developing a series of cardiac specific TG bearing selected HIV-1 genes. These TG target the selected HIV-1 genes expressed in cardiac ventricular myocytes. Tissue-specific targeting of this type enables us to define structural and functional effects of specific HIV-1 gene products on the cardiac myocyte.
艾滋病相关性心脏病，尤其是心肌病（CM），是一个日益受到认可的临床问题，其发病机制尚未明确。在艾滋病心肌病的潜在病因中，包括心肌细胞的HIV-1感染及随后的心脏功能障碍、机会性感染、炎症反应、细胞因子作用以及处方药或非法药物的心脏毒性。多种因素可能影响艾滋病心肌病的发展，这似乎是很有可能的。转基因小鼠（TG）是探索心脏功能和疾病机制的有用生物学工具。在艾滋病模型中，转基因小鼠通过体内和体外联合研究，为阐明艾滋病心肌病的机制提供了新途径。利用靶向和非靶向转基因小鼠，可以研究特定HIV-1基因产物对心脏组织的结构和功能影响。还可以确定包括治疗药物或心脏毒素在内的环境因素的影响。为了利用转基因小鼠解决艾滋病心肌病的复杂性问题，我们实验室采用了一种实验方法来模拟临床情况。我们在联合抗逆转录病毒治疗方案的心肌病模型中，利用广泛表达HIV-1基因产物的艾滋病转基因小鼠，来确定艾滋病及其治疗对小鼠心脏结构和功能的心血管影响。我们正在培育一系列携带选定HIV-1基因的心脏特异性转基因小鼠。这些转基因小鼠靶向在心室肌细胞中表达的选定HIV-1基因。这种类型的组织特异性靶向使我们能够确定特定HIV-1基因产物对心肌细胞的结构和功能影响。
