# Role of KLK10 in Endothelial Biology and Atherosclerosis

> **NIH NIH F31** · EMORY UNIVERSITY · 2020 · $45,520

## Abstract

TITLE: Role of KLK10 in Endothelial Biology and Atherosclerosis
PROJECT SUMMARY/ABSTRACT:
 Atherosclerosis is a chronic inflammatory disease of the arterial blood vessels that underlies the
occurrence of heart attack, peripheral artery disease, and ischemic stroke; the leading causes of death
worldwide. Currently cholesterol lowering statin drugs and stents are the most commonly used therapies for the
prevention and treatment of atherosclerosis, however, despite their success, atherosclerosis is still the leading
killer. Therefore, new therapeutics are needed to treat atherosclerosis. It is well known that atherosclerosis
preferentially occurs in areas of disturbed blood flow while areas of stable flow are protected from developing
atherosclerosis. Therefore, it is my goal to develop novel therapies to prevent and revert atherosclerotic diseases
by studying the role of flow-dependent genes during my PhD training. In this grant, I will look to characterize one
of the most flow-sensitive proteins, Kallikrein Related Peptidase 10 (KLK10), and its effects on atherosclerosis.
KLK10 is a serine protease that has increased expression in endothelial cells under stable blood flow, while
being dramatically reduced under disturbed blood flow conditions both in vivo and in vitro. KLK10 may also be
important for regulating the development of atherosclerosis. We have preliminary data that KLK10 is able to
lower endothelial cell inflammation and permeability, however the mechanism is unclear, and it is not known
whether these individual effects lead to an overall anti-atherogenic effect. Based on preliminary data, I
hypothesize that KLK10 inhibits endothelial inflammation, permeability, and atherosclerosis by mechanisms
dependent on the Protease Activated Receptor 1 and 2 (PAR1 and PAR2) signaling pathway. In Aim 1, I will
investigate the mechanisms by which KLK10 inhibits endothelial cell inflammation and permeability in a PAR1-
and PAR2- dependent manner. This will involve in vivo and in vitro signaling assays using recombinant KLK10
(rKLK10) and pharmacological inhibitors or siRNAs of KLK10 and PAR1/2, under static and flow conditions. In
Aim 2, I will test the ability of KLK10 to decrease atherosclerosis in vivo in a PAR1 and PAR2-dependent manner
in vivo. In order to carry out these studies, I will use the Partial Carotid Ligation (PCL) mouse model developed
in our lab, which allows us to induce disturbed blood flow and atherosclerosis in vivo. By injecting rKLK10 or
KLK10 AAV into PCL mice, I will test whether KLK10 inhibits atherosclerosis progression, in both mice WT mice
and mice without PAR1 or PAR2. These aims together will test whether KLK10 has a potential role as a
therapeutic protein for the treatment of atherosclerosis. Furthermore, we will be able to delineate one of the key
mechanisms underlying the flow-dependent development of atherosclerosis. Through this proposal, I will the
obtain the necessary PhD training in mechanical biology and vascu...

## Key facts

- **NIH application ID:** 9869705
- **Project number:** 5F31HL145974-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Darian Williams
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869705

## Citation

> US National Institutes of Health, RePORTER application 9869705, Role of KLK10 in Endothelial Biology and Atherosclerosis (5F31HL145974-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9869705. Licensed CC0.

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