Navigation Links
Double duty: Loss of protective heart failure protein causes high blood pressure
Date:5/5/2008

(PHILADELPHIA) Scientists at the Center for Translational Medicine at Thomas Jefferson University in Philadelphia have found that a protein that appears to have protective and perhaps healing effects for failing hearts also plays a similar role in high blood pressure. They found lower-than-normal levels of the protein S100A1 in cells that line blood vessel walls in animals with high blood pressure.

When the researchers, led by Patrick Most, M.D., assistant professor of Medicine at Jefferson Medical College and former postdoctoral fellow Sven Pleger, M.D., experimentally lowered the amount of S100A1 protein in the animals blood vessels, they were able to dramatically increase blood pressure. The preliminary results identified a novel and rather unanticipated biological function of the protein and suggest that S100A1 could be a therapeutic target for blood pressure treatment. The teams findings appear in the journal Circulation Research.

S100A1 seems to be a major player in the regulation of blood pressure and vascular function, says Dr. Most. The mechanisms by which this works is by producing more nitric oxide (NO) in the endothelial cells that line the vessel walls. A lack of NO enables hypertension.

According to Dr. Most, S100A1 is an alternative mechanism for increasing heart function. It directly regulates calcium circulation, which drives the contractions in the heart. Dr. Mosts laboratory has been working on S100A1s role in disease hearts for more than a decade, and together with a group led by Walter Koch, Ph.D, director of the Center for Translational Medicine, they have proven that loss of the protein causes diseased hearts to fail and that the protein is a potential target for gene therapy for heart failure.

S100A1, part of a larger family of proteins called S100, is primarily found at high levels in muscle, particularly the heart. Falling levels of S100A1 are critical in the loss of heart-pumping strength after a heart attack and play an important role in the progression to heart failure. A previous study in 1989 showed that the protein was reduced by as much as 50 percent in patients with heart failure.

In the current work, Dr. Most and colleague Andrea Eckhart, Ph.D., associate professor of Medicine at Jefferson Medical College, and their team found in both laboratory experiments and in animal models that blood vessels that lack S100A1 cannot relax as well as normal vessels. If the animal doesnt have S100A1, it has hypertension, he says. The mechanism is based more or less on the availability of nitric oxide. It seems that S100A1 also regulates calcium cycling in the endothelial cell, and calcium is needed in the endothelial cell to stimulate NO production. The loss of S100A1 impairs the calcium mobilization of the endothelial cell thats the link between less calcium, less NO, hypertension and endothelial dysfunction.

As a result, Dr. Most says, S100A1 might not only be a good therapeutic target for heart failure, but for hypertension as well. Current projections estimate that 29.2 percent of the adult population worldwide about 1.56 billion people will have hypertension by 2025. Hypertension has long been the most common risk factor for the development of congestive heart failure, affecting nearly five million Americans, many of whom have poor long-term prognoses, despite recent therapeutic advances.

The researchers plan to continue to investigate animal models of hypertension, noting that the current work was only possible because of the collaborative efforts of those in the Center for Translational Medicine and also the Department of Physiology. If the scientists find a lack of S100A1 in blood vessels, then they will develop treatments using the Centers in-house capabilities to generate viral delivery that can be tailored to express genes in endothelial cells. We will test genetically engineered animals to find out whether or not replacing S100A1 can decrease blood pressure, he notes.

In addition, the researchers will test a recently developed approach employing only a small fragment of the protein with a similar therapeutic potency. This fragment, Dr. Most explains, is 10 times smaller than the protein and allows a direct application in the bloodstream, almost like a real drug. The researchers hope that either the small protein fragment itself or a synthetic analogue will enable a novel therapeutic approach to treat both heart failure and hypertensive patients in the near future.


'/>"/>

Contact: Steve Benowitz
steven.benowitz@jefferson.edu
215-955-5291
Thomas Jefferson University
Source:Eurekalert

Related medicine news :

1. Pre-Pregnancy Diabetes Rates Have Doubled
2. Todays Working Adults Face Long Term Care Double Whammy, Says Denise Gott, Spokesperson for LTC Financial Partners, LLC
3. Abbott Reports Double-Digit Sales and Earnings Growth in First Quarter and Reaffirms Full-Year Growth Outlook
4. Combining liver cancer treatments doubles survival rates, UVA researchers find
5. Los Angeles Ronald McDonald House Doubles Lodging Capacity for Families of Hospitalized Children
6. Double binding sites on tumor target may provide future combination therapy
7. Gum Disease, HPV a Double Whammy
8. Uroplasty Plans to Double Sales Force During Fiscal 2009
9. Diabetics Face Doubled Risk of Heart Attack
10. Ford Launches Warriors in Pink Mustang for 09, Doubles Contributions To Race For The Cure
11. Diversified Clinical Services Doubles Field Management
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/16/2017)... NJ (PRWEB) , ... August 16, 2017 , ... With low back pain afflicting 8 ... know what causes its kissing cousin – upper back pain. But this equally vexing condition ... treatment options, according to Kaixuan Liu, MD, PhD , founder and president of Atlantic ...
(Date:8/16/2017)... ... August 16, 2017 , ... “Mom, God's Got This: Jamie's Story” is the creation ... with the Lord and has an insatiable appetite for God’s Word. , “I froze between ... free gifts retrieved from packages of oatmeal. I have one to this day on proud ...
(Date:8/15/2017)... Buffalo, NY (PRWEB) , ... August 15, 2017 , ... ... as maintenance treatment for multiple myeloma has been completed, with the team’s findings now ... Philip L. McCarthy, MD , Director of the Blood and Marrow Transplant Program at ...
(Date:8/15/2017)... ... 15, 2017 , ... Horizon Goodwill is honored to receive ... overwhelmed with gratitude for the very generous donation from BB&T. Our mission is ... get a job and keep it. This donation will go a long way ...
(Date:8/15/2017)... ... August 15, 2017 , ... ... to announce the 19th Annual V Foundation Wine Celebration raised nearly $9 million ... more than $7 million in “Fund-A-Need” donations to support the study of BRCA ...
Breaking Medicine News(10 mins):
(Date:8/7/2017)... , Aug. 7, 2017 Zimmer Biomet Holdings, Inc. ... today announced that its Board of Directors has approved the ... third quarter of 2017. ... on or about October 27, 2017 to stockholders of record ... Future declarations of dividends are subject to approval of the ...
(Date:8/7/2017)... 2017  Diplomat Pharmacy, Inc. (NYSE: DPLO), the nation,s largest ... June 30, 2017.  All comparisons, unless otherwise noted, are to ... Second Quarter 2017 Highlights include: ... an increase of 3.5% Total prescriptions dispensed ... of 7.5% versus 7.6% Gross profit ...
(Date:8/4/2017)... 2017 The search for test results that ... consult has long been the goal of healthcare providers ... of the largest meeting of lab professionals and IVD ... research firm Kalorama Information.  The firm said scores of ... related supplies and software were at the American Association ...
Breaking Medicine Technology: