# Hemodynamics and hepatic remodeling

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $376,875

## Abstract

SUMMARY
 The goal of this study is to understand the effects of hemodynamic changes on liver structure and
function with a focus on portal hypertension. Portal hypertension is a major complication of chronic liver
disease. Liver cirrhosis is its most common cause, but it develops in non-cirrhotic conditions as well. In portal
hypertension, portal venous flow decreases, while hepatic arterial (HA) flow increases because of a
combination of a hepatic arterial buffer response and vasodilation of splanchnic arteries. How these changes
influence liver structure and function is largely unknown.
 Our preliminary data show that rats with partial portal vein ligation (PPVL; a surgical model of portal
hypertension) develop portal tract fibrosis. PPVL partially occludes the portal vein at a pre-hepatic site and
leads to portal hypertension and increased HA-flow. Rats with PPVL also showed increased infiltration of
macrophages and T-cells in portal tracts. Further, increased blood flow is known to cause remodeling of
arterial walls, mediated by transient accumulation and activation of perivascular macrophages and T-cells.
Therefore, we hypothesize that increased HA-flow in portal hypertension facilitates portal tract fibrosis by
recruiting macrophages and T-cells through signals that are mediated by mechano-transduction. Liver
remodeling through enhanced HA-flow could also be a second hit that amplifies liver fibrosis/cirrhosis. Further,
we hypothesize that the spleen is an important source of the infiltrating immune cells.
 To test these hypotheses, we propose to examine the following three aims: 1) Determine the role of
HA-flow in the development of portal tract fibrosis and the significance of flow-induced portal tract fibrosis in the
progression of liver fibrosis/cirrhosis, 2) Determine the mechanism by which increased HA-flow causes
immune cell infiltration and portal tract fibrosis, and 3) Determine the mechanism by which immune cells
regulate portal tract fibrosis.

## Key facts

- **NIH application ID:** 10144827
- **Project number:** 5R01DK117597-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** YASUKO IWAKIRI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $376,875
- **Award type:** 5
- **Project period:** 2018-05-05 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144827

## Citation

> US National Institutes of Health, RePORTER application 10144827, Hemodynamics and hepatic remodeling (5R01DK117597-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10144827. Licensed CC0.

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