Project I

PVAT has been narrowly viewed as a tissue that feeds information to the blood vessel through secretions and homing of immune cells; this is ‘outside-in’ communication and has been considered 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.

Mission

Project I overall hypothesis is that PVAT mechanically coordinates with the blood vessel in control of vascular tone, contributing to (patho)physiological 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, cyclical pressure.

Our second hypothesis is that PVAT has a dynamic mechanical stiffness of its own that reduces vascular stiffness in health (Aim 2). We stand to redefine what is the formal blood vessel with this new knowledge.

Project I Team

Stephanie Watts

Full Professor, Dept of Pharmacology and Toxicology
Director of the PPG, Project I Leader, Core A Leader

Director of Project I. Stephanie’s contribution is to bring the smaller and seemingly disparate pieces of information into a larger, integrated picture. She also helps us stay connected to the other projects of this PPG effort, helping to feed information to and from such that the science of all projects informs that of the others.

Sara Roccabianca

Associate Professor, Dept of Mechanical Engineering
Project I Co-Leader, Project IV Collaborator

Sara is the head engineer of this project (!) and provides the knowledge needed to think about PVAT as a tissue that should be considered mechanically. She was and is essential to thinking about PVAT in this novel way.

Beth Lockwood

Assistant Professor, Dept of Pharmacology and Toxicology
Core B Leader

Beth has been a long term scientist at MSU.  Her part of Project I is to develop and use various techniques to investigate new functions of PVAT

Carolina Restini

Assistant Professor, Dept of Pharmacology and Toxicology
Core B Leader

Dr. Restini is an Associate Professor in the Dept of PHM/TOX.  Her research in the PVAT PPG pertains to understanding the function of PVAT in the renal vasculature, as well as testing he hypothesis that a microbiome exists in PVAT.  She has specific expertise in vessel contractility.

Teresa Krieger-Burke

Assistant Prof, Dept of Pharmacology and Toxicology, In Vivo Facility Director
Project I Collaborator, Core D Collaborator

Dr. Krieger-Burke will facilitate measurement of pulse wave velocity and other whole animal measures important to the PPG.

Dillon McClintock

Graduate Student
Project I member

Dillon is a graduate student in the Roccabianca lab. She is a critical part of the team building, with Core D, a new instrument that will allow us to reproducibly measure deformation and thus have a solid platform on which to build our mechanistic experiments.

Janice M. Thompson

Research Associate
Project I Member

Long term research associate of the Watts lab. Janice is dedicated to Western analyses (she excels at protein work), small vessel work +/-PVAT and RT-PCR. Her long terms knowledge of this lab and of MSU helps us be better in everything we do.

Integration with other projects

Project I is purposefully crafted to be at the center of this PPG application. By studying the whole tissue, it integrates knowledge of the neurohumoral (Project II), immune (Project III) and adipocyte potential (Project IV) into a working model.

Project I and III will work together to understand the functional impact an active (stretched) immune cell community and its environment has on the two new mechanisms studied by Project I, PVAT mechanotransduction and stiffness. Similarly, the impact of stretch on the fate of adipocyte progenitors (Project IV) parallels Project I’s commitment to understanding the effect of stretch on PVAT mechanical functioning.

We NEED our cores!

  • Core B (animal) provides all models our group uses.
  • Core C provides feedback information learned from experiments in other Projects to inform us of particular molecules/cell types we should consider in mechanotransduction and stiffness experiments.
  • Core D (microscopy) helps us take expert images.

Publications

A cell atlas of thoracic aortic perivascular adipose tissue: a focus on mechanotransducers

Janice M Thompson , Stephanie W Watts , Leah Terrian 2, G Andres Contreras , Cheryl Rockwell , C Javier Rendon , Emma Wabel  Lizbeth Lockwood , Sudin Bhattacharya, Rance Nault Am J Physiol Heart Circ Physiol 2024 May 1;326(5):H1252-H1265. doi: 10.1152/ajpheart.00040.2024. Epub 2024 Mar 22. ...

Innervation of adipocytes is limited in mouse perivascular adipose tissue

Marie Hanscom , Wilmarie Morales-Soto , Stephanie W Watts , William F Jackson , Brian D Gulbransen Am J Physiol Heart Circ Physiol 2024 Jul 1;327(1):H155-H181. doi: 10.1152/ajpheart.00041.2024. Epub 2024 May 24. ...

Integrins play a role in stress relaxation of perivascular adipose tissue

Stephanie W Watts, Janice M Thompson, Sudin Bhattacharya, Vishal Panda, Leah Terrian, Andres Contreras, Rance Nault Pharmacol Res 2024 Jun 14:206:107269. doi: 10.1016/j.phrs.2024.107269. Online ahead of print. ...

Perivascular Adipose Tissue Remodels Only after Elevation of Blood Pressure in the Dahl SS Rat Fed a High-Fat Diet

J Vasc Res. 2023 Dec 19:1-12. doi: 10.1159/000535513. Online ahead of print. Caitlin Wilson , Janice M Thompson , Leah Terrian , Adam D Lauver , Emma D Flood , Gregory D Fink , Lisa Sather , Sudin Bhattacharya , G Andres Contreras , Stephanie W Watts  ...

A Cell Atlas of Thoracic Aortic Perivascular Adipose Tissue: a focus on mechanotransducers

Janice M Thompson , Stephanie W Watts, Leah Terrian, G Andres Contreras , Cheryl Rockwell , C Javier Rendon , Emma Wabel , Lizabeth Lockwood , Sudin Bhattacharya , Rance Nault bioRxiv 2023 Oct 9:2023.10.09.561581. doi: 10.1101/2023.10.09.561581. Preprint ...

Protocols