Total Knock Out

Gene knockout may be effective treatment for diabetes-related heart failure

(RxWiki News) Silencing the TLR4 gene can stop the process that may lead to cardiovascular disease in diabetic patients, according to researchers writing in BioMed Central's Journal of Translational Medicine.

The scientists administered a series of in vitro tests indicating TLR4 plays a substantial role in hyperglycaemic cardiac apoptosis (a condition in which cardiovascular cells begin to die as a result of sustained, elevated blood-sugar levels), and that silencing the gene using specific small interfering RNA (siRNA) can prevent it.

"We found that TLR4 was up-regulated in the myocardia of diabetic mice," said Wei-Ping Min, from the University of Western Ontario, Canada. "Treatment with TLR4 siRNA attenuated the apoptosis seen in these cells, thus highlighting the potential clinical use of siRNA-based therapy."

Researchers induced hyperglycemia in adult mice by injecting them with streptozotocin (a poison to insulin-producing beta cells). After 7 days of hyperglycemia, the level of TLR4 mRNA in myocardial tissue was significantly elevated with signs evident of apoptosis (cell suicide). Silencing TLR4 suppressed so-called apoptotic cascades, marking the first demonstration of the prevention of cardiac apoptosis in diabetic mice through silencing the gene, according to Min.

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Review Date: 
December 13, 2010