'Blueprint' for blocking MMP may unlock new treatments for deadly blood infection
Researchers studying the life threatening infectious disease sepsis have discovered how the infection can lead to a fatal inflammatory response through blood vessel cells. The research, which is published in EMBO Molecular Medicine, focuses on blocking crucial Matrix Metalloprotease enzymes (MMP) which activate the response.
Sepsis, and the associated systemic inflammatory response syndrome (SIRS), is a deadly condition caused by an infection of the blood which leads to whole-body inflammation. The condition is a major cause of death in intensive care wards worldwide and is most common in elderly and critically ill patients, as well as patients who are immunocompromised.
"Sepsis is a deadly disease, yet the underlying mechanisms which allow it to change body functions remains poorly understood and this has blocked the advancement of potential treatments," said lead author Athan Kuliopulos, from Tufts Medical Center and Tufts University School of Medicine, Boston. "One such mechanism is the inability of the body to regulate the inflammatory-coagulation response to the infection, which can seriously damage the patient."
The team focused their research on Matrix Metalloprotease-1 (MMP-1) which plays a key role in the immune systems response to invading pathogens and infectious diseases, but can cause uncontrolled tissue damage, which threatens the life of patients.
The study revealed how human sepsis patients have been found to have elevated levels of proMMP-1 and active MMP-1 in blood plasma which predicted both early and late death at 7 and 28 days after diagnosis.
By studying infected mice the team examined how MMP-1 was released from endothelial cells, the thin layer of cells which cover the interior surface of blood vessels. The team found that the blocking of MMP-1 activity suppressed endothelial barrier disruption, helped prevent lung failure, and improved survival in mice.
"We made the discovery that MMP-1, and its mouse equivalent MMP-1a, activates protease-activated receptors which contribute to the pro-inflammatory response of the body to sepsis through endothelial cells," said Kuliopulos. "By blocking the mouse MMP-1 we significantly improved the survival of the mice thus demonstrating a dependence on MMP-1."
The findings reveal MMP-1 to be an important early activator and suggest that therapeutics which target MMPs may prove beneficial in the treatment of sepsis.
"Sepsis remains a common, difficult to manage and stubbornly persistent syndrome when caring for critically ill patients," said Kuliopulos. "This discovery that MMP-1 acts as an activator provides us with a blueprint to investigate entirely new types of treatment for sepsis patients."
More information: Tressel. S, Kaneider. N, Kasuda. S, Foley. C, Koukos. G, Austin. K, Agarwal. A, Covic. L, Opal. S, Kuliopulos. A, A matrix metalloprotease-PAR1 system regulates vascular integrity, systemic inflammation and death in sepsis, EMBO Molecular Medicine, Wiley-Blackwell, May 2011, DOI: 10.1002/emmm.201100145
Provided by Wiley
- How life-threatening blood clots take hold Apr 16, 2009 | not rated yet | 0
- TB discovery paves the way for drugs that prevent lung destruction Apr 25, 2011 | not rated yet | 0
- Naturally occurring enzyme can break down key part of Alzheimer's plaques Oct 24, 2006 | not rated yet | 0
- Leptin action in the brain linked to sepsis survival Apr 30, 2010 | not rated yet | 0
- Key to out-of-control immune response in lung injury found Aug 16, 2007 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
Medical research May 23, 2013 | 5 / 5 (1) | 0 |
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
Medical research May 23, 2013 | not rated yet | 0
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
Medical research May 23, 2013 | 3 / 5 (1) | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
Medical research May 23, 2013 | 5 / 5 (3) | 0 |
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
Medical research May 23, 2013 | 5 / 5 (2) | 0
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
2 hours ago | not rated yet | 4
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
2 hours ago | not rated yet | 1
(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...
1 hour ago | not rated yet | 0
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
23 hours ago | 5 / 5 (3) | 0 |
Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...
2 hours ago | not rated yet | 0
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
20 hours ago | 3.7 / 5 (3) | 2 |