Featured Research

from universities, journals, and other organizations

New pathway discovered in blood vessel inflammation and disease

Date:
September 4, 2013
Source:
Case Western Reserve University
Summary:
Researchers have identified a genetic factor that blocks the blood vessel inflammation that can lead to heart attacks, strokes and other potentially life-threatening events.

Case Western Reserve researchers have identified a genetic factor that blocks the blood vessel inflammation that can lead to heart attacks, strokes and other potentially life-threatening events.

The breakthrough involving Kruppel-like factor (KLF) 15 is the latest in a string of discoveries from the laboratory of professor of medicine Mukesh K. Jain, MD, FAHA, that involves a remarkable genetic family. Kruppel-like factors appear to play prominent roles in everything from cardiac health and obesity to metabolism and childhood muscular dystrophy.

School of Medicine instructor Yuan Lu, MD, a member of Jain’s team, led the study involving KLF-15 and its role in inflammation, which appears online this week in the Journal of Clinical Investigation. Lu and colleagues observed that KLF-15 blocks the function of a molecule called NF-kB, a dominant factor responsible for triggering inflammation.

This finding reveals a new understanding of the origins of inflammation in vascular diseases, and may eventually lead to new, targeted treatment options.

“It had been suspected that smooth muscle cells were related to inflammation, but it hadn’t been pinpointed and specifically linked to disease,” said Jain, Ellery Sedgwick Jr. Chair and director, Case Cardiovascular Research Institute at Case Western Reserve School of Medicine. Jain also is chief research officer for the Harrington Heart & Vascular Institute at University Hospitals Case Medical Center. “This work provides cogent evidence that smooth muscle cells can initiate inflammation and thereby promote the development of vascular disease.”

Smooth muscle cells are only one of two major cell types within blood vessels walls. The other cell type, endothelium, has traditionally taken the blame for inflammation, but Jain’s study suggests that both cells are critically important in the development of vascular disease.

The researchers learned that expression of this factor appeared mainly in smooth muscle cells and that levels were markedly reduced in atherosclerotic human blood vessels. To establish causality, the team generated genetically-modified mice where they deleted KLF-15 gene in smooth muscle cells.

“We expected to see more proliferation of the smooth muscle cells as this is a common response of this cell type in disease,” Lu said, first author on the paper. “Instead, we were surprised to see rampant vascular inflammation and hyper activated NF-kB, the master regulator of inflammation.”

The results offer hope for the development of specific anti-inflammatory therapies for vascular disease. Cholesterol-lowering drugs such as statins have some anti-inflammatory effects, but despite their widespread use, the burden of vascular disease remains high.

Jain’s previous research of the KLF family of genetic factors revealed regulator functions in blood vessels. KLF4 was shown to potently inhibit inflammation in the endothelium, the other major cell type in vessels. The current work is first to establish a role for these factors in smooth muscle inflammation.

“Collectively, these studies establish KLFs as a central hub regulating vascular health,” Jain said. “Boosting levels of these factors may be a particularly effective way to reduce inflammation and the development or progression of vascular diseases such as atherosclerosis.”

This research was funded by grants from the National Institutes of Health (R01HL112486-02) and American Heart Association (12SDG1205055).
###

About Case Western Reserve University School of Medicine
Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation’s top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School’s innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine.

Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report’s “Guide to Graduate Education.”

The School of Medicine’s primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. http://casemed.case.edu


Story Source:

The above story is based on materials provided by Case Western Reserve University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yuan Lu, Lisheng Zhang, Xudong Liao, Panjamaporn Sangwung, Domenick A. Prosdocimo, Guangjin Zhou, Alexander R. Votruba, Leigh Brian, Yuh Jung Han, Huiyun Gao, Yunmei Wang, Koichi Shimizu, Kaitlyn Weinert-Stein, Maria Khrestian, Daniel I. Simon, Neil J. Freedman, Mukesh K. Jain. Kruppel-like factor 15 is critical for vascular inflammation. Journal of Clinical Investigation, 2013; DOI: 10.1172/JCI68552

Cite This Page:

Case Western Reserve University. "New pathway discovered in blood vessel inflammation and disease." ScienceDaily. ScienceDaily, 4 September 2013. <www.sciencedaily.com/releases/2013/09/130904132508.htm>.
Case Western Reserve University. (2013, September 4). New pathway discovered in blood vessel inflammation and disease. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2013/09/130904132508.htm
Case Western Reserve University. "New pathway discovered in blood vessel inflammation and disease." ScienceDaily. www.sciencedaily.com/releases/2013/09/130904132508.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) — Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) — The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) — Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) — New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins