# Extracellular Vesicles and and HIV/cocaine associated cardiopulmonary dysfunction

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2020 · $473,740

## Abstract

PROJECT SUMMARY:
In general, the prolonged survival of HIV-infected patients with the use of antiretroviral (ART) therapy has
resulted in an increase in the incidence of non-infectious complications including cardio-pulmonary dysfunction.
In fact, recent reports suggest that pulmonary vascular remodeling and pulmonary hypertension (PH) precede
the airway destruction/emphysema development and that PH and COPD coexist in HIV-infected individuals.
Furthermore, IVDU has been found to be the most common risk factor of HIV-infection in the individuals
diagnosed with HIV related PH (HRPAH). Our previous findings consistently suggest augmentation of
pulmonary vascular dysfunction in HIV infected IVDUs compared to HIV-infected non-drug users or un-infected
IVDUs . Therefore, clear understanding of how the drugs of abuse and HIV-infection either alone or in
combination cause pulmonary vascular remodeling is urgently needed. Inflammation plays a crucial role in
vascular remodeling associated with chronic lung and cardiovascular diseases associated with HIV-infection.
We earlier observed significant perivascular inflammation in the lung sections from HIV- infected humans or
simian immunodeficiency virus (SIV)-infected macaques exposed to substance of abuse including increased
number of macrophages in the remodeled thickened vessels. Based on our recent preliminary findings, we
hypothesize that HIV-infection and cocaine mediated alterations in the macrophage derived extracellular
vesicles (EVs) promote pulmonary smooth muscle hyperplasia and vascular remodeling by regulating the
proliferative signaling cascades on delivery of its cargo to smooth muscle cells . This hypothesis will be tested
by pursuing four specific aims. In the first aim using RNA sequencing we will test how EV- miRnome gets
influenced on exposure of HIV-infected macrophages to cocaine. In the second aim, we will evaluate the effect
of these EVs on smooth muscle function using in-vitro cell-culture system. Third aim will be focused on
investigating the in-vivo effect of EVs on pulmonary vascular remodeling and right heart function using HIV-Tg
rat model and finally in the fourth aim we will leverage on using human samples from HIV-infected +/- cocaine
abusers to correlate the changes in EVs with cardio-pulmonary dysfunction. These studies are innovative
because to the best of our knowledge it will be the first attempt to understand the potential link between the
macrophage derived EVs and the HIV-1 and cocaine mediated disease progression. The proposed research is
significant because this will provide a critical foundation to understand the role of inflammation in the
development of HIV-1 and cocaine associated cardio-vascular dysfunction while identifying specific miRNAs in
EVs as biomarkers of the disease and /or new targets for preventive and therapeutic interventions in future.
Therefore, the proposal is directly responsive to PAS-16-018 entitled ‘HIV/AIDS High Priority Drug Abuse
Resear...

## Key facts

- **NIH application ID:** 9933855
- **Project number:** 5R01DA042715-05
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Navneet Kaur Dhillon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $473,740
- **Award type:** 5
- **Project period:** 2016-08-15 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933855

## Citation

> US National Institutes of Health, RePORTER application 9933855, Extracellular Vesicles and and HIV/cocaine associated cardiopulmonary dysfunction (5R01DA042715-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9933855. Licensed CC0.

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