Is Endothelial Dysfunction a Therapeutic Target for Peripheral Artery Disease? PRDM16 is going out on a limb

• Type of Material: Article
• Authors: Sandeep Kumar, Emory University; Aitor Andueza, Emory University; Hanjoong Jo, Emory University
• Language: English
• Date: 2021-06-25
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021, Wolters Kluwer Health
• Final Published Version (URL): http://dx.doi.org/10.1161/CIRCRESAHA.121.319448
• Title of Journal or Parent Work: CIRCULATION RESEARCH
• Volume: 129
• Issue: 1
• Start Page: 78
• End Page: 80
• Grant/Funding Information: This work was supported by funding from the National Institutes of Health grants HL119798, HL095070, and HL095070 to HJ. HJ was also supported by Wallace H. Coulter Distinguished Faculty Chair Professorship. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.
• Keywords: Editorials; INTER-SOCIETY CONSENSUS; NITRIC-OXIDE SYNTHASE; Life Sciences & Biomedicine; Peripheral Vascular Disease; Cardiovascular System & Cardiology; MANAGEMENT; Hematology; peripheral arterial disease; Cardiac & Cardiovascular Systems; ischemia; endothelial cells; transcription factor; Science & Technology

Abstract

Peripheral artery disease (PAD) is a significant global medical problem, affecting ~200 million people, including >8 million Americans, especially in the aging population 1. PAD causes claudication, ischemic pain and ulcerations, and critical limb ischemia resulting in limb loss 2, 3. It is also associated with an increased risk of heart attack and mortality rates 2-3 fold over the general population 4. Despite the alarming statistics, there is a lack of effective non-surgical medical therapies to prevent and treat PAD patients, especially those who are not eligible for invasive revascularization options. Therefore, there is a dire need to develop therapeutics to improve blood circulation to the affected limb before it leads to leg amputation or heart attacks. A significant factor in dictating the fate of clinical outcomes in PAD is the extent to which preexisting collateral arteries remodel, also known as adaptive arteriogenesis, to restore arterial flow in the ischemic limb 5. Unfortunately, the molecular mechanisms underlying the adaptive arteriogenesis process are still unclear. In this issue of Circulation Research, Craps et al. report Prdm16 (PR domain containing 16) as a transcription factor specific in the arterial wall, playing an essential role in adaptive arteriogenesis by maintaining the endothelial vasomotor function using a mouse model of PAD