The 2020 CPCR grants have been awarded to two teams of established clinician-scientists at four leading academic medical centers, supported by a collaborative research lab and computational resources at UCSF. The program’s goal is to identify biomarkers of poor response to procedures, to improve the patient prognosis and identify new targets for future drugs.
Peripheral artery disease (PAD) and abdominal aortic aneurysms (AAA) cause significant disability and mortality. Improved technologies have enabled less-invasive treatments, but their long-term effectiveness is limited and new interventions are often necessary. Multiple studies suggest certain molecules in our blood influence vascular repair and may serve as biomarkers to predict a positive, or negative, outcome.
The impact on patient lives would be enormous if researchers could identify the biological factors (biomarkers) that predict the success or failure of these procedures for individual patients. The proposed projects would enable major progress toward the ultimate development of validated tests to predict this response.
Michael Conte, MD highlights the importance of the projects: “Failure of leg bypass grafts can lead to amputation, repeat procedures, and further complications. Identifying patients who are at increased risk and defining new targets for therapy remain major unmet needs. Vascular Cures’ sponsorship allows us to collaborate across multiple institutions to bring collective expertise, advanced technologies, and a more diverse patient population to conduct this important research.”
Scott Berceli, MD, PhD adds his perspective: “Understanding the fundamental mechanisms that impact vein graft survival are critical in the development of next-generation therapies. This project will make significant strides towards this goal.”
Project 1: Identification of Biomarkers of Aortic Aneurysm Growth and Healing Following EVAR
Investigators: Edith Tzeng MD, UPMC (PI) and John Curci MD, Vanderbilt University
Currently, AAA are treated surgically with endovascular aneurysm repair (EVAR) but approximately 25% of patients still have persistent AAA growth and remain at risk for rupture – fatal 90% of the time. The AAA project will enroll 80 patients over two years, and also collect blood samples and imaging data.
Project 2: Exosomes as Key Signaling Mediators of Lower Extremity Vein-Graft Outcomes
Investigators: Michael Conte MD, UCSF and Scott Berceli MD, PhD, University of Florida
Dr. Conte and Dr. Berceli did previous CRM work that provided key insights in terms of the inflammatory response. In this study blood samples will be collected more frequently and at earlier time points after surgery, along with high-resolution ultrasound imaging. 60 patients undergoing leg bypass surgery will be enrolled.
Labs: Adam Oskowitz, MD, PhD, UCSF and Robert Raffai, PhD, UCSF & Department of Veterans Affairs
For both projects, a panel of biomarkers will be measured and correlated with adverse
outcomes post-surgery. Circulating exosomes (agents of intercellular communication, e.g. immune response) will also be isolated, studied for their cell signaling properties, and profiled using cutting-edge RNA sequencing technology.