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When cholesterol builds up in the arteries, giving rise to plaques, collagen forms a protective layer that envelops the plaques. If collagen fails to hold the plaques together, they burst, spilling out cholesterol, other fatty molecules, and blood-clotting agents — usually with disastrous consequences.

When Collagen Fails

Keck Associate Professor of Biomedical Engineering. Understanding how collagen breaks down could help scientists develop new treatments for atherosclerosis and other diseases that involve collagen, such as arthritis. Over the past eight years, Stultz has published a series of papers that have helped transform the prevailing theories on collagen, which has traditionally been thought of as a rigid, rope-like molecule.

For the past couple of decades, scientists have been trying to figure out the relationship between collagen and the enzymes, known as collagenases, that break it down in the body. Because collagen is a critical component of so many structural elements, such as bone and skin, its degradation is very carefully controlled. Structural studies that require crystallizing the protein a common technique also used to reveal the double helix structure of DNA showed that collagen is a tightly wound triple helix.

However, that structure puzzled scientists because it offers no access for collagenase enzymes to bind to and break down the protein. He did computer modeling that suggested higher temperatures, such as room or body temperature, allow some sections of the collagen molecule to unwind, becoming floppy. That structure also opens up a site that fits collagenase perfectly, allowing it to break down the protein.

To test this idea experimentally, Stultz and paper co-authors Ramon Salsas-Escat, a graduate student, and Paul Nerenberg, a recent PhD recipient, exposed room-temperature collagen to a mutated form of collagenase that only recognizes unfolded collagen. Previous studies had shown no degradation under these conditions, but Stultz and his colleagues waited longer up to six days , and found that some of the collagen was broken down. They also found that the percentage of floppy collagen molecules at any given time depends on the temperature.


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At room temperature, about one in 1, are floppy, and the number should be higher at body temperature. Over the past couple of decades, researchers have tried to develop drugs that inhibit collagenase enzymes, to prevent arterial plaques from rupturing, but no such drugs have been approved. Stultz is now screening computer databases for small molecules that could stabilize collagen in its tightly wound state, which could also help preserve collagen in arthritic joints.

Such drugs may also have an impact on cancer metastasis, because tumor cells must break down collagen in the basement membrane which lines the surfaces of organs and blood vessels before they can spread through the body. Topics: Biology , Electrical engineering and electronics , Faculty , Health sciences and technology , Research Laboratory of Electronics. In this systemic disorder, immune cells attack and inflame the membrane around joints. It also can affect the heart, lungs, and eyes.

Scleroderma: An autoimmune condition that causes scar tissue to form in the skin, internal organs including the GI tract , and small blood vessels. It affects women three times more often than men throughout life, occurring at a rate of 15 times greater for women during childbearing years. Churg-Strauss syndrome : A type of autoimmune vasculitis that affects cells in the blood vessels of the lungs, gastrointestinal system, skin, and nerves. Systemic lupus erythematosus lupus SLE : A disease that can cause inflammation of the connective tissue in every organ of the body, from the brain, skin, blood, to the lungs.

It is nine times more common in women than men. Microscopic polyangiitis : An autoimmune disease that affects cells in blood vessels in organs throughout the body. This is a rare condition. When the condition also affects the skin, it is called dermatomyositis. How do connective tissue diseases affect the lungs and breathing? Here is an overview: RA : Although RA mainly affects the joints, it can cause serious complications that affect the lungs.

These include painful breathing due to inflammation of the lung lining and shortness of breath because inflammation of the lining causes fluid to accumulate in the lungs. RA can also cause lung nodules spots called rheumatoid nodules to form. These usually do not cause symptoms.

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A more common effect of RA on the lungs is scarring of the tissue due to the inflammation. Symptoms of this may include shortness of breath , a chronic cough, weakness and fatigue. Treatment for pulmonary complications of rheumatoid arthritis includes removing excess fluid from the lungs and using medications to suppress the immune system that will decrease the inflammation in the lungs. Without treatment, lung involvement is the leading cause of death from scleroderma.

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Scleroderma can cause inflammation of the lung tissue, lung scarring, and injury to the blood vessels in the lungs. Symptoms of these include a feeling of breathlessness and fatigue. Treatment includes the use of immune-suppressing medications, regular exercise , and the use of supplemental oxygen if needed.

Genetic elimination of α3(IV) collagen fails to rescue anti-collagen B cells. - Semantic Scholar

GPA : This disease mostly affects the upper respiratory tract sinuses and nose , as well as the breathing tubes and the lung tissue by causing inflammation and damage to the blood vessels in those organs. Pulmonary symptoms include a cough that might include bloody phlegm, chest discomfort with or without shortness of breath, nose bleeds , and a persistent runny nose. Treatment for this condition is primarily the use of anti-inflammatory and immune-suppressing medications. Churg-Strauss syndrome : This condition that affects blood vessels in the lungs can have serious breathing complications.

It first presents with asthma -like symptoms, including shortness of breath and the inability to catch your breath.

Other symptoms can include coughing up blood. The lungs can also develop scarring as well as accumulate fluid.

Treatment includes the use of immune-suppressing drugs, usually prednisone. This is very effective in treating the syndrome. Pleurisy inflammation of the lining of the lung is the most common problem.