# Na+/H+ exchange in pulmonary hypertension

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $409,375

## Abstract

Pulmonary hypertension (PH) is a severely debilitating disease with no cure.
Morphometric studies revealed that the development of PH is associated with structural
remodeling of the small pulmonary arteries, characterized by thickening of the intimal
and medial layers and formation of vaso-occlusive lesions. Resistance to apoptosis in
both the endothelial and smooth muscle cells (EC and SMC, respectively) is a primary
feature of the remodeling process. Based on new preliminary data, this proposal tests
the novel hypothesis that SMC and EC survival during PH is promoted by increased
Na+/H+ exchange isoform 1 (NHE1) activity, which limits expression of the ER stress
signal, CHOP, and prevents activation of caspases, the final executioners of apoptosis.
Moreover, although many NHE1 inhibitors exhibit unwanted side effects, rimeporide has
been shown to have an improved safety profile. This proposal will test whether inhibition
of NHE1 can re-sensitize ECs and PASMCs to endogenous apoptotic signals, resulting
in de-remodeling of the pulmonary vasculature. Thus, the goals of this study are to: 1)
identify the mechanism by which NHE1 decreases CHOP in pulmonary vascular ECs
and SMCs during PH; 2) determine whether NHE1 activity and/or CHOP expression
controls EC and SMC susceptibility to apoptosis; 3) elucidate the role of increased NHE1
activity in regulating caspase activity and 4) evaluate the ability of NHE1 inhibition to
increase CHOP and reverse remodeling in PH models.

## Key facts

- **NIH application ID:** 9993991
- **Project number:** 5R01HL073859-12
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Larissa A. Shimoda
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,375
- **Award type:** 5
- **Project period:** 2003-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993991

## Citation

> US National Institutes of Health, RePORTER application 9993991, Na+/H+ exchange in pulmonary hypertension (5R01HL073859-12). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9993991. Licensed CC0.

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