# SNRK in ischemic vascular diseases

> **NIH NIH R01** · GEORGIA STATE UNIVERSITY · 2022 · $744,503

## Abstract

Project Summary
Angiogenesis is an important repair process in response to ischemia and therapeutic
angiogenesis has been the most promising therapy for treating ischemic diseases. However, it
appears that delivery of a single growth factor or cell type does not support angiogenesis
sufficiently to prevent the ischemic damage. Thus, a better understanding of the biology of
angiogenesis is necessary to identify new targets for treating ischemia diseases. Our
preliminary data show that there are markedly increased mRNA and protein levels of sucrose
non-fermenting 1 (Snf1)-related kinase (SNRK), a serine/threonine kinase, a novel member of
the AMP-activated protein kinase (AMPK)-related superfamily, in the patients with myocardial
infarction. Further, upregulated SNRK correlated with increased levels of neovascular formation
in human ischemic myocardium. Similarly, hind limb ischemia upregulates SNRK levels and
increased neovessel formation in the vasculature of skeletal muscles. The most conclusive
evidence for the essential role of SNRK in vascular genesis and angiogenesis is that global
heterozygous deletion of SNRK impaired new vessel formation in both physiological and
pathological conditions and exacerbated ischemic injury in several murine models of
angiogenesis including hind limb ischemia and left anterior descending coronary artery (LAD)
ligation in hearts. Thus, our central hypothesis is that SNRK promotes angiogenesis by
activating ITGB1-mediated EC migration and cell adhesion. This hypothesis will be tested
using gain-/loss-of-function strategies in both animal models and cultured cells. Aim 1 will
determine the role of SNRK in regulating angiogenesis, using EC-specific snrk knockout
(snrkf/f/VE-cad-Cre+/−) mice and SNRK EC-specific transgenic (snrk-TG) mice and define the
mechanism by which ischemia/hypoxia increases SNRK expression. In addition, the role of
SNRK in regulating angiogenesis will be determined using gain- and loss-of-function
approaches in cultured aortic rings and ECs. Aim 2 is to delineate the mechanism by which
SNRK increases EC migration, leading to angiogenesis by testing the hypothesis that SNRK
promotes angiogenesis by activating ITGB1-mediates EC migration and cell adhesion. The
successful completion of the proposed study will demonstrate that SNRK upregulation and its
related activation of β1 integrin (ITGB1)-mediated EC migration and adhesion is a new avenue
to treat ischemic vascular diseases. Since the formation of new blood vessels also contributes
to malignant, inflammatory, infectious and immune disorders, our proposed research may have
implications beyond ischemic vascular disease.

## Key facts

- **NIH application ID:** 10411882
- **Project number:** 5R01HL142287-04
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** Zhonglin Xie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $744,503
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10411882

## Citation

> US National Institutes of Health, RePORTER application 10411882, SNRK in ischemic vascular diseases (5R01HL142287-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10411882. Licensed CC0.

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