Lewis W
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Ann N Y Acad Sci. 2001 Nov;946:46-56.
Cardiomyopathy in AIDS (AIDS CM) is an important and prevalent clinical problem. Mechanisms of AIDS CM are not completely understood. Among the potential etiologies of AIDS CM are HIV-1, various opportunistic infections, inflammatory reactions, cytokine effects, and cardiotoxicity of prescribed or illicit drugs. The transgenic mouse (TG) offers a unique in vivo way to elucidate mechanisms of AIDS CM. Structural and functional effects of HIV-1 and specific HIV-1 gene products on heart tissue can be addressed by TGs. Selective effects of HIV-1 and antiretroviral therapy may be defined in controlled studies. We utilized AIDS TGs with generalized expression of HIV-1 gene products in CM models. We treated those TGs with individual and combined antiretroviral therapeutics (HAART) to compare cardiovascular effects of AIDS per se and its therapy. We next developed cardiac-specific TGs in which selected HIV-1 genes are driven by alpha-myosin heavy chain promoter to target the selected HIV-1 gene to the cardiac myocyte to define effects of specific HIV-1 gene products on the cardiac myocyte. Each transgenic approach is a model system that affords a distinct opportunity to explore the pathogenesis and pathophysiology of AIDS CM.
艾滋病相关性心肌病（AIDS CM）是一个重要且普遍存在的临床问题。AIDS CM的发病机制尚未完全明确。AIDS CM的潜在病因包括人类免疫缺陷病毒1型（HIV-1）、各种机会性感染、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。转基因小鼠（TG）为阐明AIDS CM的发病机制提供了一种独特的体内研究方法。通过转基因小鼠可以研究HIV-1及其特定基因产物对心脏组织的结构和功能影响。在对照研究中可以明确HIV-1和抗逆转录病毒疗法的选择性作用。我们在心肌病模型中使用了广泛表达HIV-1基因产物的艾滋病转基因小鼠。我们用单一和联合抗逆转录病毒疗法（HAART）治疗这些转基因小鼠，以比较艾滋病本身及其治疗对心血管系统的影响。接下来，我们构建了心脏特异性转基因小鼠，其中选定的HIV-1基因由α-肌球蛋白重链启动子驱动，使选定的HIV-1基因靶向心肌细胞，以确定特定HIV-1基因产物对心肌细胞的作用。每种转基因方法都是一个模型系统，为探索AIDS CM的发病机制和病理生理学提供了独特的机会。
