Lupus Research Institute Triggers Cascade of New Links—and Possible Solutions—to Early Heart Disease in People with Lupus

The Lupus Research Institute (LRI), the only organization singularly devoted to innovative science in lupus, reports that misbehavior among the cells that form the linings of blood vessels (called endothelial cells) in people with lupus puts them at dramatically increased risk for early heart disease and stroke.

Novel research funded in part by the LRI has found that there is an imbalance between death and regeneration of endothelial cells, which explains why vast sections of blood vessels can show early signs of atherosclerosis even among women in their 20s and 30s. Normally, these blood vessels are smooth and supple to encourage clear blood flow through the cardiovascular system.

Better understanding of cardiovascular disease in people with lupus is critical: The condition is a leading cause of death among the nearly 2 million Americans and millions more worldwide with this devastating and mysterious autoimmune illness.

The LRI-supported scientists who discovered the link between extensive cell death, subsequent abnormal repair of blood vessels, and premature atherosclerosis have now published an explanation for why this happens in people with lupus. In the journal Blood, lead study investigator Mariana J. Kaplan, an assistant professor of internal medicine in the Division of Rheumatology at the University of Michigan in Ann Arbor, shows how interferon-alpha, a protein naturally produced by the immune system, may be to blame. People with lupus tend to have abnormally high interferon-alpha levels in their bloodstream.

"We were trying to understand the reasons for the breakdown and rapid death of these cells, and were looking at whether the body's own mechanisms of repairing damaged blood vessels might be impaired in lupus," said Dr. Kaplan, one of several LRI-supported researchers who has studied interferon-alpha's role in lupus.

These insights may finally produce tools with which to identify people with lupus who are at particular risk for early cardiovascular disease and clot generation-even if they don't show outward symptoms of these complications. Could a drug that safely blocks interferon-alpha in lupus, for example, prevent the toxic cell build-up and clutter of debris within the blood vessels that leads to atherosclerosis and heart problems?

"The LRI's support for this valuable research may help us find a way for the lupus-prone immune system to clear away dead material. Lupus would then be milder and perhaps inactive over the long term," said Robert Caricchio, MD, assistant research professor of medicine in the Division of Rheumatology at the University of Pennsylvania Medical Center. "The LRI supports out-of -the-box thinking. If the Institute had not funded the hypothesis that led to this discovery, the initial idea would not have moved forward."

Adds LRI President Margaret Dowd: "These results confirm our mission of funding new science and new thinking that will result in new pathways and important insights into understanding this complex disease. It's critical to keep new ideas like this coming-and quickly, before the lives of more people with lupus are cut short."

Abnormal cardiovascular function in people with lupus

Ninety percent of people with lupus are women in the prime of their lives, and many are at greatly increased risk of cardiovascular disease caused by atherosclerosis. As many as a third of all women with lupus develop potentially fatal heart disease and strokes-and a disturbing number are unaware of the damage until it becomes permanent.

In the LRI study conducted by Dr. Kaplan, women in their 30s had the vascular health of 65-year-olds with coronary artery disease. "We found that the lupus patients had abnormal vascular function that was impaired to the same extent seen in the heart-disease patients-despite the fact that the lupus patients were approximately half the age of the heart-disease patients," Dr. Kaplan said.  "Even in the absence of other risk factors-smoking, high cholesterol, high blood pressure-women with lupus have a higher risk of dying young from cardiovascular events."

For more information about lupus and the Lupus Research Institute, visit www.lupusresearchinstitute.org.

About Dr. Kaplan

Mariana J. Kaplan, MD, is an internist and a rheumatologist.  Her research has focused on the role of abnormal interactions between antigen-presenting cells and T cells and aberrant apoptosis in the origin and development of lupus, and in studying mechanisms that contribute to accelerated atherosclerosis in people with this autoimmune illness.

About the Lupus Research Institute

The Lupus Research Institute leads the way to a cure for lupus by unleashing the scientific community's creativity, championing innovation, and exploring uncharted territory in lupus research.  The LRI recognizes that most major breakthroughs come from unexpected directions.  The Institute fosters and supports only the highest-ranked new science to prevent, treat, and cure this chronic autoimmune disease.

Through its National Coalition, a network of national and regional leaders in major cities across America, the LRI also works with patient groups to advocate for increased research funding, spread awareness of the severity of the disease and its complications, and push for new treatments and a cure.  The Institute maintains offices in New York, Los Angeles, and Chicago.

About Lupus

There is no known treatment or cure for lupus (systemic lupus erythematosus, or S.L.E.), a chronic, often devastating autoimmune disorder that can attack virtually any body organ and can be fatal.  It affects nearly 2 million Americans.  No new treatment has been approved for lupus in nearly 50 years.

Lupus is one of the nation's least recognized major diseases.  It is considered the prototype autoimmune disease because the body's immune system forms antibodies that can attack virtually any healthy organ or tissue, from the kidneys to the brain, heart, lungs, skin, joints, and blood.  Lupus is a leading cause of heart attack, kidney disease, and stroke among young women.