Project IV

As hypertension develops, the forces exerted by blood pressure are applied to the vessels’ structures inducing pathological changes in the cellular components of the vasculature. These changes are well described in cell populations of the vascular tunicas intima, media, and adventitia. However, there is a gap in our knowledge of hypertension’s impact on adipocytes and their progenitors in the fourth vessel layer, the tunica adiposa or perivascular adipose tissue (PVAT).

Adipocytes are the core cells of PVAT and are a crucial source of vasoactive components that support blood pressure control. The central hypothesis of Project IV is that vascular mechanical forces during hypertension limit the adipogenic capacity of adipocyte progenitors (AP) and enhance their fibrotic responses, leading to PVAT dysfunction.

about Project IV

Mission

Project IV will investigate the effects of vascular mechanical forces on PVAT function. In Specific Aim 1, we will determine how these forces interact with the stiffness of the PVAT extracellular matrix to affect the adipogenic potential of perivascular AP and govern their phenotype fate. In Specific Aim 2, we will determine how the adipogenic potential of perivascular AP cells is impacted by hypertension leading to an increase in their fibrotic fate and a reduction in PVAT adipocyte populations.

This project (IV) will provide unique mechanistic information on PVAT’s AP and adipocyte biology to support the development of 1) Project I, as these cells modify PVAT stiffness and how the tunica adiposa adapts to vascular mechanical forces; and 2) Projects II and III, as adipogenesis, lipogenesis, and fibrosis in PVAT respond to and modulate neurohumoral factors and immune cells.

We expect that elucidating the role of PVAT adipocyte progenitors and adipocytes as integrators of vascular health will redefine the role of these cells in the pathogenesis and control of hypertension.

Project IV Team

Andres Contreras

Associate Professor, ESI; Dept of Large Animal and Clinical Sciences
Project IV Leader

Director of Project IV that seeks to determine how high blood pressure driven vascular mechanical forces and structural cues alter the capacity of perivascular adipose tissue (PVAT) to exert its vasoactive functions and direct preadipocyte and adipocyte phenotypes. Dr. Contreras is a DVM with background on adipose tissue biology and will supervise the team of research assoaciates and graduate students that will develop project IV. His duties include designing experiments, mentoring students and associates, data analysis, and manuscript drafting.

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.

Jamie Bernard

Associate Professor, Dept of Pharmacology and Toxicology
Project III Collaborator, Project IV Collaborator

Jamie is our resident expert in adipose biology. She also has a particular interest in immune cells, which makes her a valuable team member for Project III. She provides consultation on experimental design and approach. She and the members of her laboratory also train students and postdocs on how to make conditioned media from PVAT for in vitro studies.

Javier Rendon

Graduate Student
Project IV Member

Javier Rendon is a DVM and a PhD student in comparative medicine and integrative biology. Javier interests include mesenchimal stem cell biology and cellular development. These interests will be further developed as he supports the advancement of Project IV

Integration with other projects

PIV will provide unique mechanistic information on PVAT’s adipocyte progenitors and adipocyte biology to support the development of:

1) Project I, as these cells modify PVAT stiffness and how the tunica adiposa adapts to vascular mechanical forces; and

2) Projects II and III, as adipogenesis, lipogenesis, and fibrosis in PVAT modulate and respond to neurohumoral factors and immune cells. We expect that elucidating the role of PVAT AP and adipocytes as integrators of vascular health will help identify nutritional or pharmacological strategies to prevent and treat hypertension.

Publications

PIEZO1 mechanoreceptor activation reduces adipogenesis in perivascular adipose tissue preadipocytes

Contreras GA, Rendon CJ, Flood E, Thompson JM, Chirivi M and Watts SW: PIEZO1 mechanoreceptor activation reduces adipogenesis in perivascular adipose tissue preadipocytes, Frontiers in Endocrin, 2022 Aug 31;13:995499. doi: 10.3389/fendo.2022.995499. eCollection 2022. PMID: 36120469 ...

Protocols

Available Soon.