Dynamic Organelle Remodeling in HIV-Associated Myocardial Disease: Mechanisms, Fibrotic Pathways, and Therapeutic...

Area of Science:

• Cardiology
• Infectious Diseases
• Molecular Biology

Background:

• People with HIV (PLWH) have a higher risk of myocardial fibrosis and diastolic dysfunction.
• Traditional cardiovascular risk factors and inflammation do not fully explain this increased cardiac burden.
• Emerging evidence points to chronic immune-metabolic stress impacting cardiomyocyte homeostasis in PLWH.

Purpose of the Study:

• To explore the role of cardiomyocyte organelle dysfunction in HIV-associated cardiomyopathy.
• To identify potential therapeutic targets for preventing cardiac remodeling in PLWH.

Main Methods:

• Review of emerging evidence on HIV-associated cardiomyopathy mechanisms.
• Focus on organelle-level disturbances including mitochondrial dysfunction, endoplasmic reticulum stress, and impaired autophagy.
• Analysis of how metabolic dysregulation, antiretroviral toxicity, and inflammation contribute.

Main Results:

• HIV-associated cardiomyopathy stems from persistent disturbances in cardiomyocyte homeostasis due to chronic immune-metabolic stress.
• Metabolic dysregulation, drug toxicity, and inflammation converge at the organelle level, causing mitochondrial dysfunction, ER stress, and autophagy impairment.
• These processes precede structural heart disease and lead to myocardial stiffening, even with viral suppression.

Conclusions:

• Myocardial remodeling in PLWH is a consequence of unresolved organelle stress.
• Interventions targeting metabolic risk factors, antifibrotic therapies, and pathways regulating mitochondria and proteostasis are promising.
• An organelle-centered approach, using imaging and biomarkers, can aid prevention in resource-limited settings.