Possible Key To Acute Aortic Dissection Diagnosis Uncovered
Discovery of the first biomarkers associated with acute aortic dissection could lead to a rapid diagnostic test for the often-fatal disorder, researchers reported at the American Heart Association’s Basic Cardiovascular Sciences Conference 2008 – Heart Failure: Molecular Mechanisms and Therapeutic Targets.
Acute aortic dissection is a tear that occurs in the lining of the aorta, the large artery that carries blood from the heart to the rest of the body.
Besides sudden chest pain that may radiate to the back, acute aortic dissection’s other symptoms include nausea, sweating and difficulty in breathing. The chest pain and other symptoms of acute aortic dissection are often confused with those of a heart attack, which complicates diagnosis and delays treatment. People commonly at risk of the disease include those with connective tissue disorders such as Marfan syndrome, an inherited, sometimes life-shortening disorder, as well as those with atherosclerotic vascular disease and high blood pressure. Patients with connective tissue disorders may not have had the diagnosis made before the dissection occurs, or the disorder may be inapparent.
“Thirty-three percent of acute aortic dissection patients die within the first 24 hours if they remain untreated because the disease is not diagnosed,” said Salah A. Mohamed, Ph.D., lead author of the study and a laboratory and group leader in the Department of Cardiac Surgery on the Luebeck campus of the University of Schleswig–Holstein in Germany. “Biomarker profiles can act as an important tool in the early diagnosis of the disease and, in turn, save lives.”
A biomarker is a biological substance that typically indicates the presence or increased risk of a disease. Researchers found four genes in acute aortic dissection patients who had significantly different levels of activity compared to other individuals studied. This specific combination of differences could lead to a rapid blood test for the disorder.
Mohamed and colleagues theorized that the cause of acute aortic dissection lay in the interaction of other proteins with the protein MS FBN1. That protein is encoded by a mutated gene linked to Marfan syndrome.
The team examined aortic tissue samples from 19 acute aortic dissection patients (average age 62) with no known connective tissue diseases; eight patients (average age 33) who carried the mutated gene for Marfan syndrome; and six patients (average age 57) without aortic disease who had undergone heart valve replacement served as a control group.
Researchers found 88 genes in the tissue of all 19 acute aortic dissection patients who had gene expression — the process that converts a gene’s encoded information into a protein — significantly different from the same genes in the Marfan patients and the control group.
Further investigation revealed that the MS FBN1 protein interacted directly with the proteins of four of the 88 genes — fibulin 1 (FBLN1), fibulin 2 (FBLN2), Decorin (DCN) and microfibrillar associated protein 5 (MFAPS5).
“Interestingly, one of these four proteins is considered as a candidate in the development of Marfan syndrome,” Mohamed said.
All four proteins are involved in building the tissue structure that surround cells in the aorta.
Two of the genes were overexpressed by at least three times, and two were underexpressed by at least the same amount. The two underexpressed genes, FBLN1 and DCN, may help explain the underlying causes of acute aortic dissection.
Underexpression of FBLN1 might weaken extracellular materials in the aorta and/or interfere with the transmission of cellular signals, thus eventually leading to acute aortic dissection. Low expression of DCN may reduce the buildup of connective tissue in the aorta.
“We did our study primarily to gain a better understanding of the molecular mechanism underlying acute aortic dissection,” Mohamed said. “The study was also aimed at the future development of a clinical test for monitoring patients with a high risk of acute aortic dissection. Most acute aortic dissection patients do not have a known connective tissue disorder. The identification of the four genes could be a starting point to develop a diagnostic tool. That, however, will require further research.”
Acute aortic dissection occurs annually in about 2,000 people in North America and about 3,000 in Europe, researchers said.