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HIV-1-Associated Left Ventricular Cardiac Dysfunction in Humanized Mice.

Prasanta K Dash¹, Fadhel A Alomar², Bryan T Hackfort³

¹Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.

Scientific Reports

|June 18, 2020

Summary

This study shows that HIV-1 infection in humanized mice causes heart failure, mimicking disease in people living with HIV-1. This model can help develop new treatments for HIV-associated heart conditions.

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Establishment of the Dual Humanized TK-NOG Mouse Model for HIV-associated Liver Pathogenesis

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Published on: September 11, 2019

Area of Science:

Immunology
Cardiology
Virology

Background:

The molecular mechanisms driving early-onset heart failure in people living with HIV-1 (PLWH) are not fully understood.
HIV-1 infection is associated with increased cardiovascular complications, including heart failure.

Purpose of the Study:

To determine if humanized NOD.Cg-Prkdc scid Il2rgt m1Wjl/SzJ (Hu-NSG) mice infected with HIV-1 can model the cardiac dysfunction seen in PLWH.
To characterize the cardiac pathology and functional deficits in HIV-1 infected Hu-NSG mice over time.

Main Methods:

Longitudinal echocardiography was used to assess cardiac function in HIV-1 infected Hu-NSG mice.
Histopathological analyses were performed on heart tissues to evaluate structural changes and cellular infiltration.

Main Results:

HIV-1 infected Hu-NSG mice developed left ventricular diastolic dysfunction, mitral regurgitation, and reduced ejection fraction.
Cardiac pathology included coronary microvascular leakage, fibrosis, and myocardial immune cell infiltration.
The observed cardiac deficits recapitulated key features of progressive heart disease in PLWH.

Conclusions:

HIV-1 infected Hu-NSG mice serve as a relevant preclinical model for studying HIV-associated heart failure.
This model can be utilized for screening potential pharmacological agents to mitigate cardiac dysfunction in PLWH.