Scholarlink

Background <p>Antiretroviral therapy (ART) in human immunodeficiency virus (HIV) markedly improved life expectancy in persons living with HIV (PLWH), but cardiac disease has emerged as the leading cause of death in this population. The prevalence of impaired diastolic function and heart failure with preserved ejection fraction (HFpEF) is higher among PLWH on ART. However, the specific role that HIV itself, and/or ART may have on the cardiomyocyte phenotype is unknown. We investigated modified molecular pathways in cardiomyocytes after exposure to serum from the <Emphasis Type="Underline">same</Emphasis> patients who were initially ART-naïve and then subsequently ART-treated.</p> Methods <p>Rat cardiomyocytes were treated for 24 hours with serum obtained longitudinally from PLWH (N = 10) before and after being on ART for 6 months. Transcriptomic changes were determined by RNA sequencing. Measures of apoptosis, calcium handling, and extracellular matrix remodeling were analyzed using TUNEL assay and western blot.</p> Results <p>Here we show that exposure to serum from ART-naïve PLWH increases cardiomyocyte cell death. In contrast, exposure to serum obtained from the same PLWH after six months on ART results in altered expression of calcium-handling proteins and upregulation of profibrotic and extracellular matrix–related markers, indicating altered contraction and relaxation, and adverse cardiac remodeling.</p> Conclusions <p>These findings demonstrate dysregulated molecular pathways in cardiomyocytes following exposure to untreated HIV serum versus ART-treated HIV serum from patients followed longitudinally. Altogether, these data suggest that HIV infection and ART contribute to changes seen in the cardiomyocyte phenotype and play complementary roles in the pathogenesis of diastolic dysfunction and HFpEF in PLWH.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Molecular insights in HIV-associated cardiac dysfunction

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月31日

查看全文
  • María Valero-Muñoz,
  • Eng Leng Saw,
  • David R. Pimentel,
  • Adam C. Gower,
  • Suman Srinivasa,
  • Markella V. Zanni,
  • Mabel Toribio,
  • Steven K. Grinspoon,
  • Flora Sam

摘要

Background

Antiretroviral therapy (ART) in human immunodeficiency virus (HIV) markedly improved life expectancy in persons living with HIV (PLWH), but cardiac disease has emerged as the leading cause of death in this population. The prevalence of impaired diastolic function and heart failure with preserved ejection fraction (HFpEF) is higher among PLWH on ART. However, the specific role that HIV itself, and/or ART may have on the cardiomyocyte phenotype is unknown. We investigated modified molecular pathways in cardiomyocytes after exposure to serum from the same patients who were initially ART-naïve and then subsequently ART-treated.

Methods

Rat cardiomyocytes were treated for 24 hours with serum obtained longitudinally from PLWH (N = 10) before and after being on ART for 6 months. Transcriptomic changes were determined by RNA sequencing. Measures of apoptosis, calcium handling, and extracellular matrix remodeling were analyzed using TUNEL assay and western blot.

Results

Here we show that exposure to serum from ART-naïve PLWH increases cardiomyocyte cell death. In contrast, exposure to serum obtained from the same PLWH after six months on ART results in altered expression of calcium-handling proteins and upregulation of profibrotic and extracellular matrix–related markers, indicating altered contraction and relaxation, and adverse cardiac remodeling.

Conclusions

These findings demonstrate dysregulated molecular pathways in cardiomyocytes following exposure to untreated HIV serum versus ART-treated HIV serum from patients followed longitudinally. Altogether, these data suggest that HIV infection and ART contribute to changes seen in the cardiomyocyte phenotype and play complementary roles in the pathogenesis of diastolic dysfunction and HFpEF in PLWH.