# BCCMA: Cardiovascular Remodeling following Arteriovenous Fistula Creation: Type VIII Collagen Contributes to Adverse Arteriovenous Fistula Remodeling

> **NIH VA I01** · MIAMI VA HEALTH CARE SYSTEM · 2024 · —

## Abstract

This BCCMA entitled “Cardiovascular Remodeling following Arteriovenous Fistula Creation” brings
together three VA investigators to elucidate the mechanisms of arteriovenous fistula (AVF) maturation failure in
the setting of chronic kidney disease (CKD). In this specific Project 2, entitled “Type VIII Collagen Contributes
to Adverse Arteriovenous Fistula Remodeling,” we plan to advance our understanding of the molecular
mechanism determining venous maturation after arteriovenous anastomosis with the hope of developing
personalized interventions to prevent early failure. Vascular access failure is the most important cause of
morbidity and hospitalization among veterans and the general population receiving hemodialysis (HD). This
highlights a clear need for in-depth research initiatives that apply state-of-the-art research technology to
clinically relevant tissues to dissect the cellular and molecular mechanisms leading to failure. This retro-
translational research (from clinical to basic science) finds support in preliminary premises that reveal the
association between alterations in extracellular matrix (ECM) composition and failure. We have recently
discovered that embryogenic type VIII collagen in the human AVF is associated with non-maturation. This
collagen promotes further matrix deposition during vascular development and fibrotic diseases. Our
fundamental hypothesis is that postoperative activation of the non-canonical TGF-b / MAPK / ELK-1 signaling
axis in venous SMC upregulates COL8A1 expression and protein accumulation to exacerbate fibrosis and
inward remodeling of the fistula wall. To test the hypothesis, we will use an integrated molecular/cellular
approach, encompassing in vivo and in vitro models. In Aim 1, we will demonstrate the causality of SMC-derived
Type VIII collagen in AVF remodeling. In Aim 2, we will dissect the molecular and cellular mechanisms by which
type VIII collagen increases the risk of AVF failure. Finally in Aim 3, we will demonstrate the relationship
between the number of COL8A1+ SMCs and the increased risk of maturation failure in patients undergoing AVF
creation in two stages. We will reveal the first cellular atlas of mature and failed human AVF fistulas obtained
at transposition. We will further confirm the association between this type of cells and AVF outcomes using a
propensity score-matched retrospective cohort of 100 human AVF samples. We expect to demonstrate the
causality of type VIII collagen to the improperly remodeled AVF wall.

## Key facts

- **NIH application ID:** 10805627
- **Project number:** 1I01BX006080-01A1
- **Recipient organization:** MIAMI VA HEALTH CARE SYSTEM
- **Principal Investigator:** Roberto Irenardo Vazquez Padron
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10805627

## Citation

> US National Institutes of Health, RePORTER application 10805627, BCCMA: Cardiovascular Remodeling following Arteriovenous Fistula Creation: Type VIII Collagen Contributes to Adverse Arteriovenous Fistula Remodeling (1I01BX006080-01A1). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/10805627. Licensed CC0.

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