Therapeutic angiogenesis in Buerger’s disease: reviewing the treatment landscape

Abstract

Thromboangiitis obliterans, also known as Buerger’s disease, is a rare inflammatory vasculitis that predominantly develops in smokers and characteristically affects the small- and medium-sized peripheral arteries and veins. Patients typically present with extremity claudication, but symptoms may progress to rest pain and tissue loss, especially in those unable to abstain from tobacco use. Unfortunately, traditional medical treatments are largely ineffective and due to the small caliber of affected vessels and lack of suitable distal targets or venous conduits, endovascular and open surgical approaches are often not possible. Eventually, a significant number of patients require major amputation. For these reasons, much research effort has been made in developing techniques of therapeutic angiogenesis to improve limb perfusion, both for atherosclerotic peripheral arterial disease and the smaller subset of patients with critical limb ischemia due to Buerger’s disease. Neovascularization in response to ischemia relies on a complex interplay between the local tissue microenvironment and circulating stem and progenitor cells. To date, studies of therapeutic angiogenesis have therefore focused on exploiting known angiogenic factors and stem cells to induce neovascularization in ischemic tissues. This review summarizes the available clinical data regarding the safety and efficacy of various angiogenic therapies, notably injection of naked DNA plasmids, viral gene constructs, and cell-based preparations, and describes techniques for potentiating in vivo efficacy of gene- and cell-based therapies as well as ongoing developments in exosome-based cell-free approaches for therapeutic angiogenesis. Plain Language Title and Summary A review of available and emerging treatments for improving blood flow and wound healing in patients with Buerger’s disease, a rare disorder of blood vessels Buerger’s disease is a rare disorder of the small- and medium-sized blood vessels in the arms and legs that almost exclusively develops in young smokers. Buerger’s disease causes inflammation in arteries and veins, which leads to blockage of these vessels and reduces blood flow to and from the extremities. Decreased blood flow to the arms and legs can lead to development of nonhealing wounds and infection for which some patients may eventually require amputation. Unfortunately, traditional medical and surgical treatments are not effective in Buerger’s disease, so other methods for improving blood flow are needed for these patients. There are several different ways to stimulate new blood vessel formation, both in humans and animal models. The most common treatments involve injection of DNA or viruses that express genes related to blood vessel formation or, alternatively, stem cell–based treatments that help regenerate blood vessels and repair wound tissue. This review explores how safe and effective these various treatments are and describes recent research developments that may lead to better therapies for patients with Buerger’s disease and other vascular disorders.

Thromboangiitis obliterans: a review

“…11 With current evidence, there are many types of treatments, both pharmacological and nonpharmacological, with the greatest evidence of results being the suspension of tobacco consumption. 2 The prognosis tends to be good for patients, although it has been reported that up to 70% of patients will experience an ischemic ulcer or necrosis. In some long-term studies it was reported that between 2.7 and 10.5% required major limb amputations; However, in a multicenter study of 224 patients, it was found that 34% of patients may require amputation 15 years after diagnosis.…”

“…1 Later, the disease was named after Leo Buerger, who in 1908 published a complete pathological description based on the amputation of a group of people, including smokers, with neuropathic pain, trophic changes in the skin and annexes such as distal coldness, loss of hair, onychodystrophy, with absence of posterior pedis and tibial pulses, lasting months to years, and which later presented with gangrene in the short term. 2,3 1919 results were found in SpringerLink, 1674 in Scopus, 1862 in PubMed and 5871 in ScienceDirect. A review of the articles found was carried out, the most current ones were analyzed in a period from 2002-2024 with emphasis on articles from the last 5 years, scientific articles from observational and analytical studies were included, with a total of 37 articles.…”

Iliac crest bone distraction surgery for the treatment of thromboangiitis obliterans of lower limbs: A cohort-prospective preliminary study

“…TAO progression will eventually lead to limb amputation. Therefore, the ideal treatment modality for TAO is still undecided and controversial [10].…”

A scope systematic review to clarify immune response to tobacco in Buerger

“…However, most are ineffective (12). Angiogenesis stimulation (13), and sympathectomy (14)are prominent surgical options in these patients, but the distal ischemic conditions have almost made these cases ineffective in the main treatment.…”