# BCCMA: Interplay of Novel Mediators of Vascular Aging Pathologies

> **NIH VA I01** · PORTLAND VA MEDICAL CENTER · 2024 · —

## Abstract

Abstract
 Vascular dementia (VaD) is the second most common cause of dementia, often triggers progressive
cognitive impairment similar to that of Alzheimer’s disease (AD). The current treatment strategies focusing on
local lesions for AD and dementia have not led to satisfactory outcomes. Therefore, comprehensively
understanding of the pathogenesis of VaD and AD is urgently required to address the unmet scientific and clinic
needs. Vascular pathologies across all vasculature have also been linked to VaD. Most notably, atherosclerosis,
stroke and hypertension accelerate the progression of cognitive impairments and dementia. Multiple large
genome-wide studies identify the atherosclerosis risk gene apolipoprotein E (APOE) as a strong genetic risk
factor for AD. However, despite shared genetic risk factors, atherosclerosis and AD are often separated in clinical
management and mechanistic studies. Pan-vascular diseases represented by coronary artery disease, ischemic
stroke, aneurysm and peripheral artery disease are all associated with VaD, thus, investigating pan-vascular
changes that impact cognitive functions may open up new avenues to understand VaD and AD. The current
application represents our long-term goals to uncover novel mechanisms linking vascular dysfunctions in the
cardio/cerebrovascular systems to VaD/AD. Our effort has led to the discovery of a new role of the Runt-related
transcription factor 2 (Runx2) in regulating both aortic and cerebral vascular functions. We and others previously
reported that Runx2 is an integral regulator for vascular calcification. Our preliminary studies identified novel
function of Runx2 in regulating atherosclerosis, arterial stiffness, cerebral blood flow and cognitive function in
mice; and uncover upregulation of Runx2 in aging, atherosclerosis and AD mice, as well as in human AD/VaD
tissues. Single cell RNA sequencing analysis further discovered a novel regulation of Runx2 on SMC phenotypic
switch, beyond promoting SMC calcification. With an array of molecular, biochemical, proteomics and
bioinformatics approaches, preliminary studies uncovered Runx2 interaction with an essential contractile SMC
regulator, serum response factor (SRF), supporting a novel Runx2/SRF regulatory network in SMC phenotypic
switch and calcification. Elucidating the novel function of Runx2 and Runx2-dependent signaling in regulating
VaD will provide new insights to fill the knowledge gaps, which may lead to novel strategies for clinical
management or treatment of VaD/AD.

## Key facts

- **NIH application ID:** 10701264
- **Project number:** 1I01BX006321-01
- **Recipient organization:** PORTLAND VA MEDICAL CENTER
- **Principal Investigator:** Yabing Chen
- **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/10701264

## Citation

> US National Institutes of Health, RePORTER application 10701264, BCCMA: Interplay of Novel Mediators of Vascular Aging Pathologies (1I01BX006321-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10701264. Licensed CC0.

---

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