The innovative target of RNA offers hope to improve the results in patients with chronic limb ischemia

Mark W. Feinberg, MD, a cardiologist with the mass general Brigham Heart and Vascular Institute and a professor of medicine at Harvard Medical School, is the older author of the article published in the Journal of Clinical Investigation, “Lncrna of smooth muscle cells” controls angiogenesis in chronic hazard Limbant by mir-143-3p/hip.

Q: What question did you study?

What causes bad results in patients with advanced peripheral arteries who develop a complication called ischemia of chronic limb (CLTI), which has a high risk of limb amputation due to the reduction of blood flow to the limbs?

For decades, many research on ctli focused on understanding the substances of factors derived from endothelium released by cells that determine our blood vessels-how these factors lead to the growth of new blood vessels. (The development of a new blood vessel of existing is called angiogenesis). The idea is that if we can find a therapy that helps patients from CLTI produce more blood vessels, we can improve blood flow to endangered limbs and reduce the risk of amputation or other health complications.

Until now, growth factors that have been identified have failed in clinical trials to improve the results. Our study indicates a different approach. We resettled in terms of factors in skeletal muscle samples from patients with CLTI to identify those that were different compared to control.

Surprisingly, these were not growth factors that appeared as different, but long-long RNA (lncrna) called Carn-i was not expressed in endothelial cells, but in smooth vascular muscles.

Q: What methods or approach did you use?

We used a number of approaches to transcriptomous profiling to identify LNCRNA CARMN in human skeletal muscles and in mouse models of limb ischemia.

We have developed a knockout mouse LnCrna Carn, which showed impaired blood flow recovery, limb necrosis and amputation in a similar way as patients with CLTI, which have reduced levels of expression of this lncrna in skeletal muscle biopsy.

Q: What did you find?

We discovered that the unique protein called HHIP, made by smooth muscle cells, is controlled by LnCrna Carn. HHIP helps in managing the growth of blood vessels, blood flow and tissue healing.

When HHip was blocked or when another molecule that controls HHIP increased the blood vessels increased, and the damaged tissue cured more effectively. This reveals a new way in which smooth muscle cells and blood vessel cells cooperate, which scientists did not understand before.

Q: What was surprising in your study?

Surprising, despite the fact that this lncrna is not expressed in endothelial cells that produce capillaries, mice that cannot produce this lncrna, have reduced capillaries in skeletal muscles with ischemia of the limbs. HHIP seems to be a missing link, combining what is happening in smooth muscle cells (SMC) with the effects that we see in endothelial cells (ECS). HHIP braking or micro -hypertension, which regulates HHIP, was sufficient to fully save angiogenesis, perfusion of limb tissue and repair.

Q: What are the implications?

The work is provided by new therapeutic strategies regarding chronic ischemia threatening the limbs and provides a new insight into the SMC-EC interrogation, which was not previously understood in the field of angiogenesis.

Q: What are the next steps?

We are trying to find out why the molecule Tanker It decreases when the blood flow is blocked in the limbs. We found a promising new goal that can control Carn when oxygen levels are low. This can lead to new ways to increase the carn, improve blood flow and help tissue treatment-benefits for people with various heart and blood vessels, such as peripheral and clti arterial disease.