# Role of Dietary Nutrients in Induction of Pseudocapillarization and the Functional Consequences for Hyperlipidemia

> **NIH NIH R56** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $338,250

## Abstract

ABSTRACT
The central tenet of this proposal is that the modern diet is enhanced in dietary nutrients due to food
preparation techniques and a shift in dietary nutrients that leads over many years leads to a process
called pseudocapillarization. Pseudocapillarization is defined as an ultrastructural change of liver
sinusoidal endothelial cells (LSECs) that is seen in aging experimental animals and also in humans
starting as early as the 4th decade of life. Pseudocapillarized LSECs also demonstrate functional changes,
specifically in their ability to endocytose certain substrates. Pseudocapillarization has been linked to
changes in serum lipids that are partially responsive or unresponsive to statin therapy and therefore
contribute to the so-called residual risk for atherosclerosis (i.e. not treatable with statins).
The overall objectives of this application are to understand the mechanisms that link dietary
enhancements to morphological and functional changes seen in LSECs in aging, to establish the impact
of these changes on hyperlipidemia, and to determine whether therapeutic strategies to reverse the aged
LSEC phenotype might be clinically beneficial.
Specific aims: aim 1 will examine possible pathways that link dietary changes to signaling that
downregulates the nitric oxide pathway in LSECs to determine the aberrant signaling that leads to
pseudocapillarization. Aim 2 will use cutting-edge methodology to re-examine the mechanism of
chylomicron remnant clearance; will examine approaches to either reverse pseudocapillarization in aged
rats or exacerbate the change in LSECs and examine the effect on post-prandial lipid profiles, lipid
clearance by LSECs, LSEC endocytosis and ultrastructure; and will examine the endocytotic machinery
involved in lipid clearance in LSECs from young rats, old rats and old rats with reversal of
pseudocapillarization.

## Key facts

- **NIH application ID:** 10674261
- **Project number:** 1R56AG071480-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** LAURIE D DELEVE
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $338,250
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10674261

## Citation

> US National Institutes of Health, RePORTER application 10674261, Role of Dietary Nutrients in Induction of Pseudocapillarization and the Functional Consequences for Hyperlipidemia (1R56AG071480-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10674261. Licensed CC0.

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