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Area of Science:

  • Cardiology
  • Molecular Biology
  • Virology

Background:

  • Cardiac disease is the leading cause of death in people living with HIV (PLWH).
  • Diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) are more prevalent in PLWH on antiretroviral therapy (ART).
  • The specific impact of HIV and ART on cardiomyocyte phenotype remains unclear.

Purpose of the Study:

  • To investigate molecular pathway modifications in cardiomyocytes exposed to serum from ART-naïve and ART-treated PLWH.
  • To understand the roles of HIV infection and ART in cardiomyocyte dysfunction.

Main Methods:

  • Rat cardiomyocytes were exposed to serum from PLWH longitudinally (before and after 6 months of ART).
  • RNA sequencing was used to analyze transcriptomic changes.
  • Apoptosis, calcium handling, and extracellular matrix remodeling were assessed via TUNEL assay and western blot.

Main Results:

  • Serum from ART-naïve PLWH increased cardiomyocyte cell death.
  • Serum from ART-treated PLWH altered calcium-handling protein expression.
  • ART-treated serum upregulated profibrotic and extracellular matrix markers, indicating adverse cardiac remodeling.

Conclusions:

  • HIV infection and ART differentially affect cardiomyocyte molecular pathways.
  • These findings suggest HIV and ART play complementary roles in the pathogenesis of diastolic dysfunction and HFpEF in PLWH.