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Gene affecting platelet activity tied to pathogenesis of CVD
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Researchers found that the messenger RNA of a platelet-related gene was lower in people with CVD than in those without it, suggesting that downregulation of the gene may be associated with CVD pathogenesis.
“It’s well described that platelets are involved in the pathogenesis of atherosclerosis and atherothrombosis,” Jeffrey S. Berger, MD, cardiologist and associate professor of medicine at NYU Langone Medical Center, told Cardiology Today. “We are constantly learning how platelets work. We don’t know how to measure platelet function very well. But we have come a very long way, and we can now identify individuals with hyperreactive platelets. The next question is, how and why are these individuals different? By studying the RNA of the platelets, we can start to understand why individuals have differences in their levels of platelet function.”
Berger and colleagues performed a microarray of RNA in platelets and found “there were many differentially expressed candidates between those with hyper- and those with normal platelet activity,” he said.
The researchers identified one gene, WD-40 repeat domain 1 (WDR1), which enhances actin-depolymerizing factor activity, that was downregulated in the platelet messenger RNA (mRNA) of individuals with platelet hyperreactivity. They sought to determine its impact on platelet function and CVD.
In the lab, Emilie Montenont, MS, a doctoral student in the divisions of cardiology and hematology of the department of medicine at NYU School of Medicine, “demonstrated that alterations of this gene affect platelet function,” Berger said in an interview. “Not only was this gene correlated in humans between those with activated vs. normal platelets, but when you induced a change in this transcript, you affected platelet function, demonstrating how important this gene is in affecting how platelets work.”
The researchers then found that patients with established CVD (n = 27) had lower expression of WDR1 than in age- and sex-matched healthy controls (n = 10; P = .0148), and a Western blot analysis confirmed that WDR1 was downregulated in the mRNA of those with CVD but not in controls (P = .0078).
“This was the first time where a gene was identified and the effect of upregulating or downregulating this gene on platelet function was tested,” Berger told Cardiology Today. “The proof of concept of this method is very novel, and it is very important for future studies. We identified a new transcript that affects platelet function and correlates with disease. It could potentially be used in the future for risk stratification or diagnosis. Future research might also evaluate whether targeting this with a therapy could impact CVD.” – by Erik Swain
For more information:
Jeffrey S. Berger, MD, can be reached at Marc and Ruti Bell Program in Vascular Biology, Cardiovascular Clinical Research Center, New York University School of Medicine, 530 First Ave., Skirball 9R, New York, NY 10016; email: jeffrey.berger@nyumc.org.
Disclosure: The study was funded primarily by the NIH. The researchers report no relevant financial disclosures.
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