# Drug abuse and HIV-associated pulmonary vascular injury

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2022 · $600,466

## Abstract

PROJECT SUMMARY
University of Kansas Medical Center Research Institute, Inc.
Advancement in antiretroviral therapy (ART) has clearly led to a serious increase in the prevalence of non-
infectious cardio-pulmonary complications among HIV-infected individuals including chronic obstructive
pulmonary disease (COPD) and HIV-related pulmonary arterial hypertension (HIV-PAH). 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. Significant
number of previous findings including from our lab consistently suggest increased risk for pulmonary vascular
dysfunction in HIV-infected individuals who abuse illicit drugs compared to HIV-infected non-drug users or un-
infected drug abusers. Understanding the mechanisms by which cocaine and HIV-1 trigger pulmonary vascular
injury is needed to develop preventive and early diagnosis strategies for patients at risk of HIV-PAH.
Pulmonary arterial smooth muscle cells (PASMCs) are one of the primary cell-types that undergo hyperplasia
during vascular remodeling. The salient finding in all our published reports is the synergistic or additive
enhancement in the proliferation of PASMCs exposed to both HIV protein(s) and cocaine. Recently, long
noncoding RNAs (LncRNAs) have emerged as important regulators of diverse biological process including cell
proliferation and apoptosis. Based on our published and recent preliminary findings we hypothesize that
alteration in the levels of lncRNA:ENST-536 in response to HIV-protein(s) and/or cocaine in smooth muscle
cells promote pulmonary vascular remodeling and cardio-pulmonary complications. In the first aim we will
examine if changes in the expression of ENST-536 lncRNA and its nearby tumor suppressive gene, HOXB13
regulate the HIV-Tat and cocaine mediated changes in the smooth muscle phenotype. In the second aim, we
will investigate how the interactions between lncRNA ENST-536 and RNA binding protein(s) (RBP) regulate
the HIV-Tat and cocaine mediated smooth muscle dysfunction.Third aim will be focused on investigating the in-
vivo role of lncRNA ENST-536 and HOXB13 in the pulmonary vascular dysfunction and right ventricular failure
using pre-clinical animal model These studies are innovative because to the best of our knowledge it will be the
first attempt to understand the potential link between the role of LncRNA, RBP and HOXB13 in the HIV-1
and/or cocaine mediated pulmonary vascular remodeling. The proposed research is significant because it will
enhance our understanding of pathogenic mechanisms involved in the development of HIV-PAH and will fulfill
the purpose of NOT-HL-19-677 (SEARCH: Stimulating ExplorAtory Research on HIV/AIDS Contribution
to Heart, Lung, Blood and Sleep Comorbidities) in search of novel mechanisms involved in HIV-associated
comorbidities.

## Key facts

- **NIH application ID:** 10330405
- **Project number:** 5R01HL152832-02
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Navneet Kaur Dhillon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $600,466
- **Award type:** 5
- **Project period:** 2021-02-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330405

## Citation

> US National Institutes of Health, RePORTER application 10330405, Drug abuse and HIV-associated pulmonary vascular injury (5R01HL152832-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10330405. Licensed CC0.

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