# Smad2 in vascular smooth muscle homeostasis

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $505,297

## Abstract

Summary/Abstract
Aberration of vascular smooth muscle cell (SMC) phenotypes cause structural defects and impaired mechanical
properties of artery wall, leading to artery stiffness, which correlates with high blood pressure and is an
independent risk factor for the resistant hypertension. It is well-known that arterial wall stiffens with aging. In
addition to hypertension, vascular aging is an independent risk factor for cardiovascular diseases including
coronary artery disease, stroke and heart failure. However, the factors and mechanisms that control vascular
aging, especially SMC aging and artery stiffness, remain largely unknown. Our exciting preliminary data
demonstrate that Smad2 plays a critical role in maintaining SMC and vascular homeostasis and blood pressure.
SMC-tissue specific deficiency of Smad2 (Smad2sm-/-) in mice causes alterations in elastin and collagen content
and structure in the vessel wall, resulting in decreased artery distensibility, increased pulse pressure (indicator
of artery stiffness), and increased mean artery pressure. The vascular wall remodeling/stiffness in Smad2 SMC-
deficient mice appears to be caused by a premature SMC aging with an elevation in p53 level. In fact, the
increase in p53 level along with the decrease in Smad2 expression in artery SMC correlates with the aging in
mouse and human. Importantly, the correlation of decreased Smad2 with increased p53 is also closely
associated with the onset of hypertension in human. These data strongly support a novel hypothesis that
Smad2 maintains vascular homeostasis and blood pressure by inhibiting p53 expression and/or activity in SMC.
Using primary culture of SMCs, in vivo Smad2 and p53 SMC-specific knockout mouse models combining with
molecular, cellular, histological, and pharmacological approaches, we will 1) test if Smad2 is essential for
maintaining the vascular wall elasticity and blood pressure homeostasis; 2) elucidate the mechanism by which
Smad2 regulates SMC homeostasis through inhibiting p53 expression/activity; and 3) determine if blockade of
p53 attenuates Smad2 deficiency-caused artery stiffness and hypertension. Successful completion of the
proposed study will establish a novel mechanism regulating SMC aging and blood pressure homeostasis. It will
also allow us to identify potential novel approaches that may be used to develop effective therapeutics for treating
aging or artery stiffness-related hypertension.

## Key facts

- **NIH application ID:** 10062643
- **Project number:** 7R01HL135854-04
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Shiyou Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $505,297
- **Award type:** 7
- **Project period:** 2016-12-12 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10062643

## Citation

> US National Institutes of Health, RePORTER application 10062643, Smad2 in vascular smooth muscle homeostasis (7R01HL135854-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10062643. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*