# PVAT mechanics in health and disease

> **NIH NIH P01** · MICHIGAN STATE UNIVERSITY · 2022 · $333,981

## Abstract

Project Summary – Project I
 PVAT has been narrowly viewed as a tissue that communicates with the blood vessel through secretions
and homing of immune cells. This is `outside-in' communication and is a passive function of PVAT. We
hypothesize that to maintain the homeostasis so critical to tissue health, there must be an `inside-out'
communication from the formally accepted vessel layers – intima, media, adventitia – to the PVAT that is
mechanical in nature. This allows the blood vessel to inform PVAT of its status, such that PVAT can respond
appropriately to maintain homeostasis. Thus, if secretions are made by PVAT, this may not be
uninformed/passive, but rather in response to messages received from the blood vessel it surrounds. Project I
overall hypothesis is that PVAT mechanically coordinates with the blood vessel in control of vascular
tone, contributing to (patho)physiological function.
 We propose investigation of two (2) functions of PVAT that have not been previously considered and which
exert profound effects on vascular function. Our first hypothesis is that pressure is transmitted to PVAT
through mechanosensitive elements (Aim 1). Of all the adipose tissues in the body, PVAT is primed to be
mechanoresponsive because it is exposed to constant pressure. Second, we hypothesize that PVAT has a
dynamic mechanical stiffness of its own that reduces vascular stiffness in health (Aim 2). Further, changes in
this dynamic stiffness occur with disease (e.g. increased stiffening). We share preliminary data that support
both hypotheses. PVAT, in healthy tissue, is integral to the vessel reduced vessel tone and stiffness. Thus,
this understudied vessel layer must be considered as a clinically relevant tissue. Two aims focus individually
on these new parameters. We will integrate information from other projects in how innervation and
neurotransmitters (Project II), immune cells (Project III), and direct influence of stretch on adipocyte/SVF
function (Project IV) impact PVAT mechanotransduction (Aim 1) and stiffness (Aim 2) in health. Core B
provides high fat (HF) diet-induced hypertension (Dahl S with non-hypertensive Dahl R control) as well as a
novel mid-thoracic aorta coarcted model to impose elevated pressure independent of diet. Core C has and will
continue to provide RNA sequencing analysis for determination of specific cell types within PVAT that support
mechanotransduction. Core D will be of marked assistance in measuring non cellular contributions made by
collagens and elastin. When these gaps are filled, our work will justify that PVAT should always be considered
an active partner of the formal blood vessel. We stand to redefine what is the formal blood vessel with
this new knowledge.

## Key facts

- **NIH application ID:** 10331578
- **Project number:** 1P01HL152951-01A1
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Stephanie W Watts
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $333,981
- **Award type:** 1
- **Project period:** 2021-12-22 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10331578

## Citation

> US National Institutes of Health, RePORTER application 10331578, PVAT mechanics in health and disease (1P01HL152951-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10331578. Licensed CC0.

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