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Certain anticancer agents could be harmful to patients with heart disease
Date:6/23/2008

ing process is important not just in the early development of the heart, but also in adult hearts to maintain cardiac blood vessels. They found that completely blocking hedgehog signaling in the hearts of adult mice caused many small coronary blood vessels to disappear, leaving heart muscle short of oxygen and leading to heart failure. In mice with experimentally induced heart attacks, mildly inhibiting hedgehog signaling led to a worsening of their heart conditions.

"We gave mice small amounts of antibodies against hedgehog, and in those that had a recent myocardial infarction (heart attack), this led to poorer heart function and some lethality," explains Lavine. "We've shown that small decreases in the hedgehog pathway in the setting of heart disease can lead to deleterious outcomes, and since a number of patients with cancer also have heart disease, this raises concern for those who might be treated with hedgehog antagonists."

Studies suggest that abnormal activation of the hedgehog pathway is implicated in many different types of cancer, and drugs that impede hedgehog signaling are being tested against several of these cancers, including basal cell carcinoma (a type of skin cancer), prostate cancer, pancreatic cancer, colorectal cancer and medulloblastoma (a type of brain tumor). These trials are still in the early stage.

The current study was the first demonstration that hedgehog signaling is essential to maintain a healthy supply of blood vessels in heart muscle in adult organisms.

"Nobody had ever looked for hedgehog signaling in the adult heart before," says Ornitz. "Kory discovered that the hedgehog signaling pathway is a mechanism to regulate the heart's vasculature by influencing growth factors that promote blood vessel growth. The body can tune the hedgehog pathway to modulate its signal and increase and decrease blood vessels on demand, providing a mechanism to ensure a constant supply of oxygenated blood for the ene
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Contact: Gwen Ericson
ericsong@wustl.edu
314-286-0141
Washington University School of Medicine
Source:Eurekalert

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