New Therapeutic Target Identified for Chronic Limb-Threatening Ischemia

A recent study uncovers a new therapeutic target involving a long non-coding RNA in smooth muscle cells, promising improved treatments for chronic limb-threatening ischemia and related vascular conditions.
Recent research has uncovered a groundbreaking potential treatment pathway for patients suffering from chronic limb-threatening ischemia (CLTI), a severe complication of peripheral artery disease that often leads to limb amputation due to inadequate blood flow. The study, conducted by researchers from Mass General Brigham and Harvard Medical School, highlights the significance of a long non-coding RNA (lncRNA) called CARMN, which is uniquely expressed in vascular smooth muscle cells rather than endothelial cells.
In their investigation, scientists performed extensive transcriptomic profiling on skeletal muscle samples from patients with CLTI and resulted in the discovery that CARMN plays a crucial role in regulating a protein known as HHIP, produced by smooth muscle cells. HHIP influences blood vessel growth, tissue repair, and blood flow. Modulating HHIP levels in mouse models demonstrated improved angiogenesis and tissue healing, revealing a novel interaction between smooth muscle cells and endothelial cells that was previously unrecognized.
The researchers developed a knockout mouse lacking CARMN, which showed impaired blood flow recovery, tissue necrosis, and limb amputation—mirroring the clinical features of CLTI patients with reduced CARMN expression. Interestingly, inhibiting HHIP or increasing microRNAs that target HHIP was sufficient to promote angiogenesis and tissue repair, indicating promising therapeutic strategies.
Importantly, despite CARMN not being expressed in endothelial cells responsible for capillary formation, mice lacking this lncRNA exhibited fewer capillaries in ischemic limbs, emphasizing the pivotal role of HHIP as a mediator in SMC-EC crosstalk. Blocking HHIP or boosting related microRNAs effectively rescued blood vessel growth and limb function.
This research opens new avenues for treating CLTI by targeting smooth muscle cell signaling pathways. Future studies aim to understand how CARMN expression is reduced during ischemia and to identify ways to enhance its activity, potentially offering better outcomes for patients with limb-threatening vascular conditions. These insights could contribute to novel therapies that not only improve blood flow but also accelerate tissue healing in vascular diseases.
Source: https://medicalxpress.com/news/2025-09-treatment-chronic-limb-threatening-ischemia.html
Stay Updated with Mia's Feed
Get the latest health & wellness insights delivered straight to your inbox.
Related Articles
Understanding Recurring Sinus Polyps and Effective Treatment Strategies
Recent research uncovers the cellular mechanisms behind persistent sinus polyps and highlights new targeted therapies, offering hope for better management of chronic rhinosinusitis. source: https://medicalxpress.com/news/2025-09-sinus-polyps-tackle.html
Immune Tolerance Achieved in iPS Cell-Derived Neural Transplants for Parkinson's Disease
Recent clinical research highlights the successful use of allogeneic iPSC-derived neural progenitors in Parkinson's disease, demonstrating immune tolerance and reduced rejection risks, advancing regenerative medicine for neurodegenerative disorders.
Understanding How Candida albicans Colonizes the Human Gut
New research uncovers the mechanisms behind Candida albicans' ability to colonize the human gut, highlighting potential targets to prevent fungal overgrowth and associated health risks.
Research Finds No Evidence Supporting Fasting Before Surgery to Prevent Postoperative Vomiting
Recent research indicates that fasting before surgery does not reduce the risk of aspiration or vomiting, challenging traditional guidelines and potentially improving patient comfort.



